Abstract:
:Recently, apoptosis has been implicated as one of the end points of cells exposed to chemotherapeutic agents. The p53 and Bcl-2 family of proteins are involved in chemotherapy-induced apoptosis, but in a cell type-dependent manner. We sought to determine the roles played by the p53 and Bcl-2 family of proteins in 5-fluorouracil (5-FU)-induced apoptosis of human colon cancer cell lines. We first studied the p53 genetic and functional status, and then 5-FU, at inhibitory concentration of 50% (IC50) doses, was used to induce apoptosis, which was confirmed by morphological analysis and enzyme-linked immunosorbent assay (ELISA). Bcl-2, Bcl-X(L), Bax, Bad, Bak and p53 protein expression was analysed by Western blotting. Using five human colon cancer cell lines, we found that equitoxic (IC50) doses of 5-FU induced apoptosis in both wild-type p53 and mutant p53 cells. Analysis of the steady-state levels of Bcl-2 family proteins showed high expression of Bcl-X(L) in all of the cell lines except Colo320. Bcl-2 was expressed in two of them. Bax presented with the lowest basal expression and Bad showed homogeneous expression. On the other hand, Bak expression varied more than fivefold among these cells. In cells containing wild-type p53 (e.g. LoVo), 5-FU-induced apoptosis was accompanied by increased expression of Bax and Bak without consistent modulation of other bcl-2 family proteins. In contrast in cells containing mutant p53 (e.g. DLD1), Bak expression was remarkably increased. There was a significant correlation between chemosensitivity and Bcl-X(L) to Bax ratio, rather than Bcl-2 to Bax. In conclusion, these results suggest that some members of the Bcl-2 family of proteins, in human colon cancer cell lines, are modulated by 5-FU and that the ratio of Bcl-X(L) to Bax may be related to chemosensitivity to 5-FU.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Nita ME,Nagawa H,Tominaga O,Tsuno N,Fujii S,Sasaki S,Fu CG,Takenoue T,Tsuruo T,Muto Tdoi
10.1038/bjc.1998.617subject
Has Abstractpub_date
1998-10-01 00:00:00pages
986-92issue
8eissn
0007-0920issn
1532-1827journal_volume
78pub_type
杂志文章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:BACKGROUND:Earlier studies have shown raised risks of leukaemia and non-Hodgkin lymphoma in children, teenagers and young adults resident either at birth or diagnosis in Seascale. Some increases in cancer risk in these age groups have also been noted among those living around Dounreay. We aimed to update previous analy...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.357
更新日期:2014-10-28 00:00:00
abstract::Experimental studies indicated that long-chain polyunsaturated fatty acids may increase sensitivity of mammary tumours to several cytotoxic drugs. To evaluate this hypothesis in breast cancer, we have prospectively studied the association between levels of fatty acids stored in breast adipose tissue and the response o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690281
更新日期:1999-04-01 00:00:00
abstract::Associations between work in the electrical and electronic industry and cancer incidence were assessed using data for 371 890 cancers registered in England between 1981 and 1987, of which 7981 were in electrical workers. Proportional registration ratios (PRRs) were calculated, both with and without the commonest cance...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.167
更新日期:1996-04-01 00:00:00
abstract::Several diseases are known or suspected to be associated with altered levels of hormones and growth factors that may influence breast cancer risk. To elucidate this possibility, we studied the relationship between 23 medical conditions or procedures and breast cancer risk by means of data from a multicentric case-cont...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.289
更新日期:1997-01-01 00:00:00
abstract::There is increasing evidence that the presence of a systemic inflammatory response plays an important role in survival following curative resection for colorectal cancer. The present study evaluated the relationship between C-reactive protein concentrations and survival in a cohort of patients receiving adjuvant 5-flu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603185
更新日期:2006-06-19 00:00:00
abstract::Several radiotherapeutic schedules compatible with continued structural-functional integrity of the gastrointestinal (GI) mucosa were compared utilizing the P815X2 murine mastocytoma grown as a solid subcutaneous tumour. Both the tumour and underlying normal tissues were irradiated during the treatments. The tumour ex...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.29
更新日期:1975-02-01 00:00:00
abstract::Promoter region hypermethylation and transcriptional silencing is a frequent cause of tumour suppressor gene (TSG) inactivation in many human cancers. Previously, to identify candidate epigenetically inactivated TSGs in renal cell carcinoma (RCC), we monitored changes in gene expression in four RCC cell lines after tr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604180
更新日期:2008-01-29 00:00:00
abstract:BACKGROUND:Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are commonly used antihypertensives. Recently, these drugs have been associated with a protective effect against pancreatic cancer, but data on this putative association remain limited. Thus, the objective of this study...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.375
更新日期:2017-01-03 00:00:00
abstract:BACKGROUND:Activated anaplastic lymphoma kinase (ALK) gene fusions are recurrent events in a small fraction of colorectal cancers (CRCs), although these events have not yet been exploited as in other malignancies. METHODS:We detected ALK protein expression by immunohistochemistry and gene rearrangements by fluorescenc...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.401
更新日期:2015-12-22 00:00:00
abstract:BACKGROUND:This study was done to investigate the long-term event free and overall survival of high-dose chemotherapy followed by autologous stem cell transplantation (ASCT), compared to maintenance chemotherapy (MT). Patterns of recurrences and late sequelae of both arms were analysed. METHODS:A randomised open label...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/s41416-018-0169-8
更新日期:2018-08-01 00:00:00
abstract::Monoclonal antibody MUC 2-63 recognises neurogenic tumours and has been used successfully for radioimaging human malignant gliomas. We now show that the MUC 2-63 antigen has the same tissue distribution and molecular weight range as the CD44 antigen and confirm the identity of these two molecules in blocking studies u...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.402
更新日期:1994-11-01 00:00:00
abstract::It has been suggested that World War II influenced breast cancer risk among Norwegian women by affecting adolescent growth. Diet changed substantially during the war, and the reduction in energy intake was assumed to be larger in non-food-producing than in food-producing municipalities. In the present study, we have l...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600084
更新日期:2002-02-01 00:00:00
abstract::Monoclonal antibodies to carcinoembryonic antigen (CEA) promise improved specificity for the measurement of this widely expressed human cancer antigen. A mouse monoclonal antibody binds weakly to CEA in perchloric acid extracts of tumour but strongly to CEA similarly isolated from serum, and its spectrum of cancer det...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.1
更新日期:1981-01-01 00:00:00
abstract:BACKGROUND:There have been controversies in prognostic impact of mucinous histology on colorectal cancer, and its implication in patients treated with adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) is unclear. METHODS:Stage II and III colorectal cancer patients who underwent curative resection followed ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.232
更新日期:2013-05-28 00:00:00
abstract:BACKGROUND:BRCAness is defined as shared tumour characteristics between sporadic and BRCA-mutated cancers. However, how to exactly measure BRCAness and its frequency in breast cancer is not known. Assays to establish BRCAness would be extremely valuable for the clinical management of these tumours. We assessed BRCAness...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.144
更新日期:2013-05-28 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:BACKGROUND:Vegetable and/or fruit intakes in association with hepatocellular carcinoma (HCC) risk have been investigated in case-control studies conducted in specific European countries and cohort studies conducted in Asia, with inconclusive results. No multi-centre European cohort has investigated the indicated associ...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2014.654
更新日期:2015-03-31 00:00:00
abstract::The formation of cyclic AMP was studied in normal liver, subcutaneous hepatomas derived from MH1C1 cells, and premalignant liver and primary hepatomas induced by the carcinogens 2-acetylaminofluorene (AAF) and 4-dimethylamino-azobenzene (DAB). While only very slight effects of prostaglandins (PG) were seen in slices o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.281
更新日期:1978-12-01 00:00:00
abstract::Primary liver cancer (PLC) incidence trends from Africa are unknown. Using Kampala Cancer Registry data from 1960 to 1980 and 1991 to 2005, we identified 771 PLCs. Although rates were stable among men, PLC incidence among women increased >50%. Investigations of viral hepatitis, aflatoxin, obesity, and human immunodefi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604893
更新日期:2009-03-10 00:00:00
abstract::Endocrine therapy is a recognised option in the treatment of chemo-resistant ovarian cancer. We conducted a nonrandomised phase II evaluation of combination endocrine therapy with tamoxifen and goserelin in patients with advanced ovarian cancer that had recurred following chemotherapy. In total, 26 patients entered th...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6602752
更新日期:2005-09-19 00:00:00
abstract::Animal experiments remain essential to understand the fundamental mechanisms underpinning malignancy and to discover improved methods to prevent, diagnose and treat cancer. Excellent standards of animal care are fully consistent with the conduct of high quality cancer research. Here we provide updated guidelines on th...
journal_title:British journal of cancer
pub_type: 杂志文章,实务指引
doi:10.1038/sj.bjc.6605642
更新日期:2010-05-25 00:00:00
abstract::Using a panel of ten polymorphic markers, we examined the frequency of loss of heterozygosity (LOH) on chromosome 17 in 55 sporadic ovarian tumours. LOH on 17p and 17q was observed to be 50% and 62% respectively. LOH at D17S5 was detected in 24/36 (67%) of malignant cases and in 19/43 (44%) at TP53; the marker D17S855...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.594
更新日期:1996-11-01 00:00:00
abstract::Records of approximately 310,000 patients admitted to the 10 hospitals in Botswana between 1960 and 1972 have been studied and details of 1445 patients with malignant tumours abstracted. For the 894 tumours for which there was some supporting evidence--at best histological proof and minimally a clinical description of...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.138
更新日期:1975-07-01 00:00:00
abstract::A partially purified fraction of the water soluble photosensitive dye sulphonated aluminium phthalocyanine (AlSPc) was encapsulated in liposomes which were then linked to a targeting monoclonal antibody 791T/36 using a heterobifunctional linking agent. The photocytotoxic effects of the liposomes were determined on two...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.73
更新日期:1989-03-01 00:00:00
abstract::During the period 1943-1980 a significant increase in the incidence of neuroblastoma was seen in Denmark. The incidence increased from a level corresponding to that in Finland to a level corresponding to that in the USA, and the increase appears to be continuing. The increase relates to children aged under 5 years, an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1986.270
更新日期:1986-12-01 00:00:00
abstract:BACKGROUND:Testing for high-risk human papillomavirus (HPV) in primary screening for cervical cancer is considered more sensitive, but less specific, in comparison with Pap-smear cytology. Women with persistent HPV infections have a higher risk of developing cervical intraepithelial neoplasia 2+ (CIN2+) lesions. This s...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2011.277
更新日期:2011-08-23 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::Preclinical models that can accurately predict outcomes in the clinic are much sought after in the field of cancer drug discovery and development. Existing models such as organoids and patient-derived xenografts have many advantages, but they suffer from the drawback of not contextually preserving human tumour archite...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/s41416-019-0672-6
更新日期:2020-03-01 00:00:00
abstract::Fifteen human glioma cell lines were examined for their sensitivity to 1,3-bis(chloroethyl)-nitrosourea (BCNU, carmustine) and cis-dichlorodiamminoplatinum (cisplatin), the induction of DNA interstrand cross-linking (DNA-ISC) induced by the two agents and cellular O6-alkylguanine alkyltransferase (ATase) activity. Cel...
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