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 genetically related pair of human melanoma cell lines, derived from the same patient at different stages of disease, we analysed differences in the cytokine-mediated regulation of gelatinase B (MMP-9), an enzyme thought to play an important role in cellular invasiveness, and TIMP-1, a physiological inhibitor of this enzyme. Whereas the advanced stage (i.e. metastatic) partner of this pair (WM 239) could produce gelatinase B upon induction with interleukin (IL)-1beta or tumour necrosis factor alpha (TNF-alpha), the early stage (i.e. primary) partner (WM 115) could not. In sharp contrast, we found that TIMP-1 displayed an opposite pattern of induction in these cell lines. Specifically, the early stage cell line, WM 115, demonstrated a marked increase in the production of TIMP-1 when treated with IL-1beta or TNF-alpha whereas the advanced cell line, WM 239, showed no such increase. Treatment with the DNA demethylating agent, 2-deoxy-5-azacytidine, resulted in a marked up-regulation of both gelatinase B and TIMP-1 in both cell lines. It was further found that constitutive overexpression of gelatinase B in WM 239 cells and an additional melanoma cell line (MeWo), derived from a metastatic lesion, was able to greatly enhance lung colonization in an experimental metastasis assay while we did not observe differences in tumorigenicity. From these results we conclude that an altered responsiveness of gelatinase B and TIMP-1 to induction by similar agents is associated with disease progression in human melanoma and that this altered responsiveness can have consequences to the aggressive nature of the disease.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
MacDougall JR,Bani MR,Lin Y,Muschel RJ,Kerbel RSdoi
10.1038/sj.bjc.6690385subject
Has Abstractpub_date
1999-05-01 00:00:00pages
504-12issue
3-4eissn
0007-0920issn
1532-1827journal_volume
80pub_type
杂志文章abstract::To: (1) estimate the prevalence of clinically significant emotional distress in patients attending a cancer outpatient department and (2) determine the associations between distress and demographic and clinical variables, we conducted a survey of outpatients attending selected clinics of a regional cancer centre in Ed...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6603626
更新日期:2007-03-26 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:British journal of cancer
pub_type: 已发布勘误
doi:10.1038/s41416-020-0830-x
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abstract:BACKGROUND:Subgroup analyses of clinical studies suggest that bevacizumab plus XELOX is effective and tolerable in elderly patients with metastatic colorectal cancer (mCRC). The prospective BECOX study examined the efficacy and safety of bevacizumab plus XELOX, followed by bevacizumab plus capecitabine in elderly patie...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
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abstract::Overexpression of the MDR1 product, P-glycoprotein (Pgp), has been shown to be one of the mechanisms underlying the development of multidrug resistance (MDR). Recently, one mutant p53 has been shown to stimulate the MDR1 gene promoter in vitro, whereas wild-type p53 repressed this activity. We measured Pgp and p53 exp...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1995.329
更新日期:1995-08-01 00:00:00
abstract::During the COVID-19 era, Chinese hospitals have developed a system that enables vulnerable cancer patients to continue to receive high-quality medical care, optimising their survival whilst protecting them. This includes use of digital quick codes, fever clinics and optimal scheduling. We wish to share our experiences...
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doi:10.1038/s41416-020-0856-0
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abstract::Alternative splicing of survivin mRNA gives rise to multiple isoforms, that is, survivin and 3 splice variants, survivin-2B, survivin-3B and survivin-DeltaEx3. The aim of this study was to compare the expression of survivin, survivin-2B and survivin-DeltaEx3 in normal breast tissue, fibroadenomas, primary breast cance...
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pub_type: 杂志文章
doi:10.1038/sj.bjc.6602314
更新日期:2005-01-17 00:00:00
abstract::High levels of loss of distal markers on 17p13.3 in breast cancer suggested the presence within the region of at least one tumour-suppressor gene. Here we describe the derivation of two biallelic polymorphisms from the 17p telomeric yeast artificial chromosome (YAC) TYAC98. Polymerase chain reaction-restriction fragme...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.449
更新日期:1996-09-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.40
更新日期:2015-03-31 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::In premenopausal women with advanced breast cancer the luteinising hormone-releasing hormone agonist goserelin (Zoladex, ICI plc) will produce serum levels of oestradiol equivalent to those following surgical oophorectomy or the menopause. This paper reports our further experience of using this drug in 75 premenopausa...
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pub_type: 杂志文章
doi:10.1038/bjc.1990.397
更新日期:1990-11-01 00:00:00
abstract:BACKGROUND:The Dutch guidelines advise to start radiation therapy (RT) within 5 weeks following breast-conserving surgery (BCS). However, much controversy exists regarding timing of RT. This study investigated its effect on 10-year disease-free survival (DFS) in a Dutch population-based cohort. METHODS:All women diagn...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.159
更新日期:2017-07-11 00:00:00
abstract:BACKGROUND:Non-persistence to oral hormonal therapy (HT) in breast cancer (BC) is an emerging health issue, and estimations vary according to the population selected and/or the statistical method applied. This study aimed to estimate non-persistence over 5 years to HT in an unselected sample of women with BC using a Fr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.276
更新日期:2016-10-11 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.173
更新日期:2014-05-27 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.80
更新日期:2012-04-24 00:00:00
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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
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.59
更新日期:1996-02-01 00:00:00
abstract::Benzoporphyrin derivative monoacid ring A (BPD-MA, verteporfin) is currently under investigation as a photosensitizer for photodynamic therapy (PDT). Since BPD exhibits rapid pharmacokinetics in plasma and tissues, we assessed damage to tumour and muscle microvasculature when light treatment for PDT was given at short...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6690271
更新日期:1999-04-01 00:00:00
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doi:10.1038/s41416-018-0357-6
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.238
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pub_type: 杂志文章,评审
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journal_title:British journal of cancer
pub_type: 杂志文章
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.173
更新日期:2013-05-28 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600214
更新日期:2002-04-08 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1990.56
更新日期:1990-02-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6603925
更新日期:2007-09-03 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1996.434
更新日期:1996-09-01 00:00:00
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.167
更新日期:1992-05-01 00:00:00
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pub_type: 杂志文章,多中心研究
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journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0907-6
更新日期:2020-08-01 00:00:00