Abstract:
BACKGROUND:Malignancy alters cellular complex lipid metabolism and membrane lipid composition and turnover. Here, we investigated whether tumorigenesis in cancer-derived prostate epithelial cell lines influences protein kinase C-linked turnover of ethanolamine phosphoglycerides (EtnPGs) and alters the pattern of ethanolamine (Etn) metabolites released to the medium. METHODS:Prostate epithelial cell lines P4E6, LNCaP and PC3 were models of prostate cancer (PCa). PNT2C2 and PNT1A were models of benign prostate epithelia. Cellular EtnPGs were labelled with [1-(3)H]-Etn hydrochloride. PKC was activated with phorbol ester (TPA) and inhibited with Ro31-8220 and GF109203X. D609 was used to inhibit PLD (phospholipase D). [(3)H]-labelled Etn metabolites were resolved by ion-exchange chromatography. Sodium oleate and mastoparan were tested as activators of PLD2. Phospholipase D activity was measured by a transphosphatidylation reaction. Cells were treated with ionomycin to raise intracellular Ca(2+) levels. RESULTS:Unstimulated cell lines release mainly Etn and glycerylphosphorylEtn (GPEtn) to the medium. Phorbol ester treatment over 3h increased Etn metabolite release from the metastatic PC3 cell line and the benign cell lines PNT2C2 and PNT1A but not from the tumour-derived cell lines P4E6 and LNCaP; this effect was blocked by Ro31-8220 and GF109203X as well as by D609, which inhibited PLD in a transphosphatidylation reaction. Only metastatic PC3 cells specifically upregulated Etn release in response to TPA treatment. Oleate and mastoparan increased GPEtn release from all cell lines at the expense of Etn. Ionomycin stimulated GPEtn release from benign PNT2C2 cells but not from cancer-derived cell lines P4E6 or PC3. Ethanolamine did not stimulate the proliferation of LNCaP or PC3 cell lines but decreased the uptake of choline (Cho). CONCLUSIONS:Only the metastatic basal PC3 cell line specifically increased the release of Etn on TPA treatment most probably by PKC activation of PLD1 and increased turnover of EtnPGs. The phosphatidic acid formed will maintain a cancer phenotype through the regulation of mTOR. Ethanolamine released from cells may reduce Cho uptake, regulating the membrane PtdEtn:PtdCho ratio and influencing the action of PtdEtn-binding proteins such as RKIP and the anti-apoptotic hPEBP4. The work highlights a difference between LNCaP cells used as a model of androgen-dependent early stage PCa and androgen-independent PC3 cells used to model later refractory stage disease.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Schmitt J,Noble A,Otsuka M,Berry P,Maitland NJ,Rumsby MGdoi
10.1038/bjc.2014.457subject
Has Abstractpub_date
2014-10-14 00:00:00pages
1646-56issue
8eissn
0007-0920issn
1532-1827pii
bjc2014457journal_volume
111pub_type
杂志文章abstract::Melanoma is one of the most aggressive types of cancer and resection of the tumour prior to dissemination of tumour cells is still the most effective treatment. Therefore, early diagnosis of melanocytic lesions is important and identification of novel (molecular) markers would be helpful to improve diagnosis. Moreover...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602612
更新日期:2005-06-20 00:00:00
abstract::Exploring the fundamental mechanisms behind the low tumour uptake of labelled monoclonal antibodies (MoAbs) during in vivo immunotargeting, experiments were performed to estimate the in vivo value of the association constant (Ka) in an experimental targeting reaction. An artificial tumour model was utilised, based on ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.219
更新日期:1992-07-01 00:00:00
abstract::To understand genetic events which play a role in the development and/or progression of human endometrial cancer, we studied allelotypes on all autosomal chromosomes, as well as chromosome X, with 42 microsatellite markers and 56 endometrial cancers. The most frequent loss of heterozygosity (LOH) was observed on the l...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.663
更新日期:1996-12-01 00:00:00
abstract::Human papillomavirus (HPV) is thought to cause some vulval squamous cell carcinomas (VSCC) by degrading p53 product. Evidence on whether HPV-negative VSCC results from p53 mutation is conflicting. We performed immunohistochemistry for p53 product on 52 cases of lone vulval intraepithelial neoplasia (VIN), 21 cases of ...
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析,多中心研究
doi:10.1038/sj.bjc.6600677
更新日期:2003-01-27 00:00:00
abstract::Leukaemia L 1210 cells preincubated in vitro with neuraminidase preparations derived either from Vibrio cholerae (VCN) or Clostridium perfringens (CPN) lost their i.p. transplantability for normal DBA/2 mice. This loss of transplantability could not be observed when the enzyme treated cells were implanted in mice whos...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1973.14
更新日期:1973-02-01 00:00:00
abstract::The distribution of labelled cells through 5 different mouse tumours was measured after a single injection of [3H]-thymidine [( 3H]-TdR) or [3H]-deoxyuridine [( 3H]-UdR). All the tumours had areas where the percentage of labelled cells (the labelling index, LI) was high and areas where the LI was very low. The total a...
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
abstract::Insulin-like growth factors (IGFs) I and II are implicated in progression of various tumours including colorectal carcinomas. To interfere with the production of IGFs, we treated male nude mice bearing xenografts of HT-29 human colon cancer with various potent growth hormone-releasing hormone (GH-RH) antagonists. Twic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1223
更新日期:2000-05-01 00:00:00
abstract::Ninety-nine patients with advanced breast cancer were randomized to receive either cyclophosphamide continuously or a combination of cyclophosphamide, methotrexate, 5-fluorouracil and vinblastine given intermittently. The number and duration of objective responses were greater in patients receiving the combination but...
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.1975.284
更新日期:1975-12-01 00:00:00
abstract::The Type 1 family of growth factor receptors includes epidermal growth factor receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4. Overexpression of the first two members is associated with poorer prognosis in patients with breast carcinoma. In this study we examined the expression of c-erbB-4 protein using the monoclona...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.1999.1057
更新日期:2000-03-01 00:00:00
abstract:BACKGROUND:Cabazitaxel is approved for treatment of castration-resistant metastatic prostate cancer. The current dosing strategy of cabazitaxel is based on body surface area (BSA). Body surface area is known as a poor predictor for total systemic exposure to drugs, since it does not take into account variability in act...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.91
更新日期:2017-05-09 00:00:00
abstract::A study is presented of all cases of primary sarcoma of bone registered during the period 1946 to 1974 for a specified population resident in south-western England. Ninety-six per cent of the 365 cases were histologically and radiologically verified and are separated into 8 categories of sarcoma. The number of tumours...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.221
更新日期:1977-10-01 00:00:00
abstract:BACKGROUND:Circulating tumour cells (CTCs) can be assessed through a minimally invasive blood sample with potential utility as a predictive, prognostic and pharmacodynamic biomarker. The large heterogeneity of melanoma CTCs has hindered their detection and clinical application. METHODS:Here we compared two microfluidi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0750-9
更新日期:2020-03-01 00:00:00
abstract::Although it is generally accepted that proteolytic degradation is an important mechanism used by malignant cells in the process of metastasis, comparatively little is known about the regulation of molecules responsible for proteolysis and how they become de-regulated during human tumour progression. Using a geneticall...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690385
更新日期:1999-05-01 00:00:00
abstract:BACKGROUND:The germline BRCA2 mutation is associated with increased prostate cancer (PrCa) risk. We have assessed survival in young PrCa cases with a germline mutation in BRCA2 and investigated loss of heterozygosity at BRCA2 in their tumours. METHODS:Two cohorts were compared: one was a group with young-onset PrCa, t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605822
更新日期:2010-09-07 00:00:00
abstract::Resistance of tumour cells to methylating and monochloroethylating agents in vitro and in vivo has been linked to levels of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT). In a clinical trial of temozolomide in advanced malignant melanoma, the relationship between pretreatment MGMT levels in biop...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1998.654
更新日期:1998-11-01 00:00:00
abstract::Women with a family history of breast cancer generally self-refer because they have a feeling that their risk is high. However, they have, in general, only a hazy notion of the population risk of breast cancer and their own risk in relation to this. It is probable that they are helped by genetic counselling and, if at...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.423
更新日期:1994-11-01 00:00:00
abstract::Microsatellite instability is present in over 80% of the hereditary non-polyposis colorectal carcinoma and about 15-20% of the sporadic cancer. Microsatellite instability is caused by the inactivation of the mismatch repair genes, such as primarily hMLH1, hMSH2. To study the mechanisms of the inactivation of mismatch ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600148
更新日期:2002-02-12 00:00:00
abstract::The work presented here has concerned the study of early, as well as late, enzymic changes occurring during diethylnitrosamine-induced hepatocarcinogenesis and liver regeneration after partial hepatectomy in comparison with normal liver differentiation. Rank correlation analysis of the enzyme data suggested a step-wis...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1983.222
更新日期:1983-10-01 00:00:00
abstract:BACKGROUND:Cancer prognostic biomarkers have shown disappointing clinical applicability. The objective of this study was to classify and estimate how study results are overinterpreted and misreported in prognostic factor studies in oncology. METHODS:This systematic review focused on 17 oncology journals with an impact...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0305-5
更新日期:2018-11-01 00:00:00
abstract:BACKGROUND:New prognostic markers are needed to identify patients with Ewing sarcoma (EWS) and osteosarcoma unlikely to benefit from standard therapy. We describe the incidence and association with outcome of circulating tumour DNA (ctDNA) using next-generation sequencing (NGS) assays. METHODS:A NGS hybrid capture ass...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-018-0212-9
更新日期:2018-08-01 00:00:00
abstract::We have determined the methylation status of the CpG island of the oestrogen receptor alpha gene in seven human ovarian cell lines. Cell lines expressing oestrogen receptor alpha showed no evidence of hypermethylation. In three of four cell lines that produced no detectable oestrogen receptor alpha protein, hypermethy...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600028
更新日期:2002-01-21 00:00:00
abstract:BACKGROUND:Accumulating evidence demonstrates high levels of aldehyde dehydrogense (ALDH) activity in human cancer types, in part, because of its association with cancer stem cells. Whereas ALDH1A1 and ALDH7A1 isoforms were reported to associate with prostate tumorigenesis, whether other ALDH isoforms are associated wi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.201
更新日期:2014-05-13 00:00:00
abstract::Immunoreactive and bioassayable plasma fibronectin (opsonic α(2) surface-binding (SB) glycoprotein) was measured during experimental Sarcoma-180 tumour growth in mice. Male C57BL/6 mice were challenged s.c. with 2 × 10(6) viable Sarcoma-180 tumour cells and evaluated sequentially in parallel with saline-injected contr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.174
更新日期:1980-06-01 00:00:00
abstract:BACKGROUND:The role of different subtypes of tumour infiltrating lymphocytes (TILs) in breast ductal carcinoma in situ (DCIS) is still poorly defined. This study aimed to assess the prognostic significance of B and T lymphocytes and immune checkpoint proteins expression in DCIS. METHODS:A well characterised DCIS cohor...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0797-7
更新日期:2020-05-01 00:00:00
abstract::Bilateral kidney ligation of mice immediately before injection of misonidazole (MIS) prolongs the plasma half-life of this radiosensitizer from about 2 h (in normal mice) to 10-11 h, similar to that in man. Kidney ligation does not, however, change the relative proportions of MIS and its O-demethylated metabolite, Ro-...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1979.55
更新日期:1979-03-01 00:00:00
abstract::The ESPAC-1, ESPAC-1 plus, and early ESPAC-3(v1) results (458 randomized patients; 364 deaths) were used to estimate the effectiveness of adjuvant 5FU/FA vs resection alone for pancreatic cancer using meta-analysis. The pooled hazard ratio of 0.70 (95% CI=0.55-0.88) P=0.003, and the median survival of 23.2 (95% CI=20....
journal_title:British journal of cancer
pub_type: 杂志文章,meta分析,多中心研究
doi:10.1038/sj.bjc.6604838
更新日期:2009-01-27 00:00:00
abstract::Monoclonal antibodies to epithelial-cell antigenic determinants, labelled with 123I and 125I, were administered parenterally to immunodeficient mice bearing human tumours derived from a human cancer cell line. Anterior, posterior and lateral radioscans of the body were taken with a gamma scintillation camera at variou...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1982.157
更新日期:1982-07-01 00:00:00
abstract::The cytochrome P450 CYP1B1 is consistently overexpressed in tumour cells as compared to their normal counterparts, but its precise role in drug resistance is yet to be defined. It has been reported that transfection of CYP1B1 results in increased resistance to docetaxel in V79 cells (McFadyen et al, 2001). In this stu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604195
更新日期:2008-02-12 00:00:00
abstract::Tumour-associated angiogenesis is partly regulated by the hypoxia-inducible factor (HIF) pathway. Endocrine tumours are highly vascularised and the molecular mechanisms of their angiogenesis are not fully delineated. The aim of this study is to evaluate angiogenesis and expression of HIF-related molecules in a series ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602245
更新日期:2005-01-17 00:00:00
abstract::Eighteen patients with inoperable hepatocellular carcinoma (HCC) were treated with intrahepatic arterial yttrium-90 microspheres. All these patients showed a lung shunting below 15% and a tumour-to-normal ratio higher than 2 as determined by diagnostic technetium-99m macroaggregated albumin (Tc-MAA) gamma scintigraphy...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1994.436
更新日期:1994-11-01 00:00:00