Abstract:
:Expression of both P-glycoprotein (P-gp) and mutant p53 have recently been reported to be associated with poor prognosis of breast cancer. The expression of P-gp is associated in vitro and in vivo with cross-resistance to several anti-cancer drugs. p53 plays a regulatory role in apoptosis, and mutant p53 has been suggested to be involved in drug resistance. Interestingly, in vitro experiments have shown that mutant p53 can activate the promoter of the MDR1 gene, which encodes P-gp. We investigated whether p53 and P-gp are simultaneously expressed in primary breast cancer cells and analysed the impact of the co-expression on patients prognosis. Immunohistochemistry was used to investigate P-gp expression (JSB-1, C219) and nuclear p53 accumulation (DO-7) in 20 operable chemotherapy untreated and 30 locally advanced breast cancers undergoing neoadjuvant chemotherapy with doxorubicin and cyclophosphamide. Double immunostaining showed that P-gp expression and nuclear p53 accumulation often occur concomitantly in the same tumour cells. A correlation between p53 and P-gp expression was found in all 50 breast cancers (P = 0.003; Fisher's exact test). P-gp expression, nuclear p53 accumulation, and co-expression of p53 and P-gp were more frequently observed in locally advanced breast cancers than in operable breast cancers (P = 0.0004, P = 0.048; P = 0.002 respectively. Fisher's exact test). Co-expression of p53 and P-gp was the strongest prognostic factor for shorter survival by multivariate analysis (P = 0.004) in the group of locally advanced breast cancers (univariate analysis: P = 0.0007). Only 3 out of 13 samples sequentially taken before and after chemotherapy displayed a change in P-gp or p53 staining. In conclusion, nuclear p53 accumulation is often associated with P-gp expression in primary breast cancer, and simultaneous expression of p53 and P-gp is associated with shorter survival in locally advanced breast cancer patients. Co-expression of P-gp and mutant p53 belong to a series of molecular events resulting in a more aggressive phenotype, drug resistance and poor prognosis.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Linn SC,Honkoop AH,Hoekman K,van der Valk P,Pinedo HM,Giaccone Gdoi
10.1038/bjc.1996.316subject
Has Abstractpub_date
1996-07-01 00:00:00pages
63-8issue
1eissn
0007-0920issn
1532-1827journal_volume
74pub_type
杂志文章abstract::Erbicin is a human anti-ErbB2 single-chain antibody fragment with high affinity and selectivity for ErbB2-positive cancer cells. Two anti-ErbB2 immunoconjugates, called Erb-hRNase and Erb-hcAb, have been prepared and found to be selectively cytotoxic on ErbB2-positive cancer cells in vitro and vivo. In Erb-hRNase, Erb...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604022
更新日期:2007-11-19 00:00:00
abstract::A brief account is given of two types of rare soft tissue sarcoma of uncertain histogenesis. The danger of mistaking the epitheloid sarcoma for a benign lesion is emphasized. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1971.58
更新日期:1971-09-01 00:00:00
abstract::The fluorometric microculture cytotoxicity assay (FMCA) was employed for analysing the effect of different chemotherapeutic drug combinations and their single constituents in 44 cases of acute myelocytic leukaemia (AML). A large heterogeneity with respect to cell kill was observed for all combinations tested, the inte...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1993.178
更新日期:1993-05-01 00:00:00
abstract:BACKGROUND:The PI3K/Akt signalling pathway, induced by epidermal growth factor receptor (EGFR) and Her-2, is involved in the constitutive activation of NF-kappaB in prostate cancer cell lines. In this study, we extended the in vitro observation using an ex vivo model of prostate cancer tissues and assessed the prognost...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605571
更新日期:2010-03-30 00:00:00
abstract:BACKGROUND:The role of processed meat in the aetiology of several cancers was explored in detail. METHODS:In the time period 1996-2004, a multisite case-control study was conducted in Montevideo, Uruguay. The study included 6 060 participants (3 528 cases and 2 532 controls) corresponding to cancers of the oral cavity...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2012.433
更新日期:2012-10-23 00:00:00
abstract::To examine the hypothesis that colorectal carcinomas with and without TP53 mutations may be characterised by aetiological heterogeneity, we analysed a group of 107 patients with primary Dukes' C colorectal cancer seen at the Memorial Sloan-Kettering Cancer Center (MSKCC) from 1986 to 1990. We assessed p53 overexpressi...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.171
更新日期:1995-04-01 00:00:00
abstract::Initial glycosylation of mucin-type O-linked protein is catalysed by one of the UDP-GalNAc: polypeptide N-acetyl-galactosaminyl transferase-3 (GalNAc-T3). O-glycosylation is important in the binding of cell adhesion molecules, cell differentiation, invasion, and metastasis in tumours. This study was designed to detect...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6601531
更新日期:2004-01-26 00:00:00
abstract::This study was undertaken to determine the prevalence of anti-cardiolipin antibodies (ACLAs) in patients with malignancy and to investigate a possible association of ACLAs with thromboembolic events in such patients. The study included 216 patients with solid and non-solid malignancies and an age-matched control group...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.353
更新日期:1995-08-01 00:00:00
abstract::Members of the public are increasingly consulted over health care and research priorities. Patient involvement in determining cancer research priorities, however, has remained underdeveloped. This paper presents the findings of the first consultation to be conducted with UK cancer patients concerning research prioriti...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603662
更新日期:2007-03-26 00:00:00
abstract::In the family reported here, a mother and both of her children developed a Wilms tumour, and all three tumours were of the relatively rare monomorphous epithelial histopathological subtype. Using restriction fragment length polymorphism analysis, both sibs were shown to inherit the same maternal allele from the 11p13 ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.210
更新日期:1994-06-01 00:00:00
abstract::Germline mutations in the LKB1 (STK11) gene (chromosome sub-band 19p13.3) cause characteristic hamartomas and pigmentation to develop in patients with Peutz-Jeghers syndrome. Peutz-Jeghers syndrome carries an overall risk of cancer that may be up to 20 times that of the general population and Peutz-Jeghers patients ar...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690323
更新日期:1999-04-01 00:00:00
abstract::Accuracy in the assessment of performance status by oncologists has not been well evaluated. We investigated possible discrepancies in the assessment of performance status among patients, nurses, and oncologists, and evaluated the prognostic importance of each assessment. Two hundred and six inpatients with inoperable...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.2162
更新日期:2001-11-30 00:00:00
abstract::The therapeutic efficacy of gemcitabine, a new nucleoside analogue, was assessed in a variety of well-established human soft tissue sarcoma and ovarian cancer xenografts grown s.c. in nude mice. Tumour lines selected had different histological subtypes, growth rates and sensitivities to conventional cytostatic agents....
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1993.285
更新日期:1993-07-01 00:00:00
abstract::The combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN-alpha) has reported activity in the treatment of advanced colorectal carcinoma. Laboratory studies of IFN-beta suggest that this agent may offer theoretical advantages over IFN-alpha in combination with 5-FU. A total of 27 patients with advanced or rec...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/bjc.1997.69
更新日期:1997-01-01 00:00:00
abstract::Capecitabine is an oral prodrug of 5-fluorouracil (FU). Since FU concentrations achieved in malignant lesions are an important determinant of efficacy, we investigated the intratumoral transcapillary transfer of capecitabine and its metabolites in vivo. A total of 10 patients with skin metastases from breast cancer re...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600809
更新日期:2003-03-10 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:BACKGROUND:Childhood cancer survival estimates from developing nations are rare. METHODS:Using the US SEER and the Manila and Rizal Cancer Registry databases in the Philippines, 5-year survival for childhood leukaemia and lymphoma in 2001-2005 among Asian Americans were compared with both Filipinos and Caucasians in t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605703
更新日期:2010-06-29 00:00:00
abstract::This study evaluates the efficacy of capecitabine using data from a large, well-characterised population of patients with metastatic colorectal cancer (mCRC) treated in two identically designed phase III studies. A total of 1207 patients with previously untreated mCRC were randomised to either oral capecitabine (1250 ...
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/sj.bjc.6601676
更新日期:2004-03-22 00:00:00
abstract::Metabolic reprogramming towards aerobic glycolysis is a common feature of transformed cells and can be driven by a network of transcription factors. It is well established that c-Myc and hypoxia-inducible factor-1α (HIF-1α) contribute to metabolic reprogramming by driving the expression of glycolytic target genes. Mor...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.2015.360
更新日期:2015-12-01 00:00:00
abstract::The purpose of the study is to test the hypothesis that expression of cell cycle regulatory proteins p16(INK4a) and pRb is significantly associated with prognosis in ovarian carcinomas. We performed immunohistochemical analysis of p16(INK4a) and pRb expression and correlated with survival in a series of 300 patients w...
journal_title:British journal of cancer
pub_type: 杂志文章,随机对照试验
doi:10.1038/sj.bjc.6603531
更新日期:2007-01-29 00:00:00
abstract::Extramammary Paget's disease is a particular form of skin cancer of unknown histogenesis. To look for the genetic defects underlying the pathogenesis of this tumour, we have examined loss of heterozygosity (LOH), p53 and human papillomavirus (HPV) status, and the expression of c-erbB-2 and bcl-2 proteins in 14 cases. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.482
更新日期:1997-01-01 00:00:00
abstract:BACKGROUND AND AIMS:The serum/plasma proteome was explored for biomarkers to improve the diagnostic ability of CA19-9 in pancreatic adenocarcinoma (PC). METHODS:A Training Set of serum samples from 20 resectable and 18 stage IV PC patients, 54 disease controls (DCs) and 68 healthy volunteers (HVs) were analysed by sur...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605764
更新日期:2010-07-27 00:00:00
abstract:BACKGROUND:Early detection of non-small-cell lung cancer (NSCLC) and accurate prognostic risk assessment could improve patient outcome. We examined the significance of urinary N(1), N(12)-diacetylspermine (DiAcSpm) in the detection and prognostic stratification of NSCLC patients. METHODS:A DiAcSpm/cutoff ratio (DASr) ...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.2015.349
更新日期:2015-11-17 00:00:00
abstract::Serine proteases, such as alpha-chymotrypsin or elastase, caused an aggregation of rat ascites tumour cell lines, AH-130, AH-109A and YS, in a protein free medium which preserved the cell viability. This aggregation, which was monitored spectrophotometrically, was dependent upon the protease activities and was resista...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.339
更新日期:1990-10-01 00:00:00
abstract::The association between breast and endometrial cancer was investigated in a cohort consisting of 60,065 subjects (99% of all women in whom a first breast cancer was diagnosed in Sweden in 1960-63 and 1968-81). Complete follow-up until 1981 revealed a total of 260 endometrial cancers, as against an expected number of 1...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1987.16
更新日期:1987-01-01 00:00:00
abstract::Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) blocks basic fibroblast growth factor (FGF-2)-dependent cell proliferation of a human breast epithelial line (HBL100), suggesting its potential role as a potent antiangiogenic substance. The derived cell line (HH9), which was transformed with t...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.451
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND:A combination of S-1 and cisplatin has been shown to be effective with acceptable safety for the first-line treatment of far-advanced gastric cancer in Japan. This is the first randomised phase II trial to compare S-1+paclitaxel with S-1+cisplatin in this setting. METHODS:Patients with unresectable and/or r...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/bjc.2012.222
更新日期:2012-06-26 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 development of resistance to vincristine, actinomycin D and cisplatin has been examined in a human epidermoid lung carcinoma xenograft line (HXL 55) growing in nude mice. Treatment of HXL 55 with 1 mg kg-1 vincristine or 0.5 mg kg-1 actinomycin D once in each in vivo passage resulted in a rapid reduction in tumour...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1988.155
更新日期:1988-07-01 00:00:00
abstract::Breast cancer is the second most common cancer among women in Madras and southern India after cervix cancer. The Madras Metropolitan Tumour Registry (MMTR), a population-based cancer registry, collects data on the outcome of cancer diagnosis by both active and passive methods. A total of 2080 cases of invasive female ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1997.137
更新日期:1997-01-01 00:00:00