Abstract:
:Angiogenesis is an essential requirement for tumour growth and metastasis and is regulated by a complex network of factors produced by both stromal cells and neoplastic cells within solid tumours. The cytokine tumour necrosis factor alpha (TNF-alpha) and the enzyme thymidine phosphorylase (TP) are two factors known to promote tumour angiogenesis. We have demonstrated recently that high numbers of tumour-associated macrophages (TAMs) are significantly associated with increased tumour angiogenesis and poor prognosis in invasive carcinoma of the breast. We have also shown that TAMs are a major source of TNF-alpha in invasive breast carcinomas, and that macrophage-like stromal cells as well as tumour cells synthesize TP in such tumours. However, little is known of the factors that regulate the production or activity of these factors in the tumour microenvironment. As TNF-alpha has been shown to up-regulate TP expression in tumour cells in vitro we performed an immunohistochemical study to investigate the possibility that TNF-alpha may be involved in the regulation of TP expression by malignant breast epithelial cells in vivo. To do this, we used a cocktail of non-neutralizing monoclonal anti-TNF-alpha antibodies to visualize both TNF-alpha-expressing macrophages and TNF-alpha bound to its receptors on tumour cells and endothelial cells in a series of 93 invasive carcinomas of the breast. A semiquantitative grading system was then used to compare these staining patterns with that for TP in the same biopsies. TNF-alpha immunoreactivity was also compared with various important tumour variables known to relate to outcome in this disease (microvessel density, node status, grade, stage, receptor status and macrophage infiltration), as well as relapse-free and overall survival data for these patients. Our data show significant positive correlations between TNF-alpha bound to its receptors on tumour cells and: (1) TP protein production by tumour cells, and (2) axillary lymph node status (i.e. metastasis). These results suggest that tumour cell responsiveness to TNF-alpha produced by neighbouring TAMs may play a part in the regulation of TP expression by tumour cells as well as their metastatic behaviour. This may explain, in part, the relationship between increased macrophage infiltration and angiogenesis in breast cancer, and further supports the contention that TAMs may represent an important target for future anti-angiogenic therapies.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Leek RD,Landers R,Fox SB,Ng F,Harris AL,Lewis CEdoi
10.1038/bjc.1998.373subject
Has Abstractpub_date
1998-06-01 00:00:00pages
2246-51issue
12eissn
0007-0920issn
1532-1827journal_volume
77pub_type
杂志文章abstract:BACKGROUND:Cediranib is a highly potent inhibitor of vascular endothelial growth factor (VEGF) signalling with activity against all three VEGF receptors. Bevacizumab is an anti-VEGF-A monoclonal antibody with clinical benefit in previously treated metastatic colorectal cancer (mCRC). METHODS:Patients with mCRC who had...
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.2012.545
更新日期:2013-02-19 00:00:00
abstract:BACKGROUND:The Mediterranean diet has been shown to have a beneficial role on various neoplasms, but data are scanty on pancreatic cancer. METHODS:We analysed data from two case-control studies conducted in Italy between 1983 and 2008, including 362 and 326 pancreatic cancer cases and 1552 and 652 hospital-controls, r...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.345
更新日期:2013-09-03 00:00:00
abstract::The lymphocyte marker pattern of non-Hodgkin's lymphoma cells was related to current concepts of lymphoma classification. In a series of 28 lymphomas lymphocyte markers indicated that 2 were of histiocytic origin, 2 were unclassifiable, none were derived from T cells and the remainder were B-cell neoplasms. The immuno...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1977.154
更新日期:1977-07-01 00:00:00
abstract::Oestrogen receptor (ER) is used routinely to predict endocrine responsiveness in patients with breast cancer. A second ER, ERbeta has been described but its significance remains undefined; most studies have described mRNA levels rather than protein expression. Here, we demonstrate for the first time, immunohistochemic...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1721
更新日期:2001-04-20 00:00:00
abstract::Trastuzumab has significantly improved the overall survival of patients with HER2+ metastatic breast cancer (MBC). However, outcomes can vary, with patients progressing within 1 year of treatment or exceptional cases of complete response to trastuzumab for ≥10 years. Identification of the underlying genomic aberration...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0999-z
更新日期:2020-10-01 00:00:00
abstract::The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 maligna...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2001.1899
更新日期:2001-09-01 00:00:00
abstract::Bispecific antibodies (bsAb) are considered as promising tools for the elimination of disseminated tumour cells in a minimal residual disease situation. The bsAb-mediated recruitment of an immune effector cell in close vicinity of a tumour cell is thought to induce an antitumoural immune response. However, classical b...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1237
更新日期:2000-07-01 00:00:00
abstract:BACKGROUND:Soft tissue sarcomas are heterogeneous and a major complication in their management is that the existing classification scheme is not definitive and is still evolving. Leiomyosarcomas, a major histologic category of soft tissue sarcomas, are malignant tumours displaying smooth muscle differentiation. Althoug...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2016.280
更新日期:2016-10-11 00:00:00
abstract:BACKGROUND:The poor prognosis of patients with colorectal-cancer liver metastases (CRLM) and the insufficiency of available treatments have raised the need for alternative curative strategies. We aimed to assess the therapeutic potential of TL-118, a new anti-angiogenic drug combination, for CRLM treatment, in a mouse ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.322
更新日期:2012-08-07 00:00:00
abstract::Selection of patients for randomised clinical trials may have a large impact on the applicability of the study results to the general population presenting the same disorder. However, clinical characteristics and outcome data on non-entered patients are usually not available. The effects of patient selection for the E...
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.6600514
更新日期:2002-09-09 00:00:00
abstract::Both misonidazole (MISO) and hyperthermia are known to enhance the radiation response of hypoxic cells, and to be selectively cytotoxic against cells in a hypoxic and acidic environment. The ability of these conditions to modify the effect of irradiation and their individual relationship was studied in a C3H mammary c...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1980.2
更新日期:1980-01-01 00:00:00
abstract::Bleomycin is a chemotherapuetic drug used primarily in the treatment of squamous-cell carcinoma, while misonidazole is an effective radiosensitizer and potent cytotoxic agent selectively affecting hypoxic cells. V79 Chinese hamster cells were used to investigate the cytotoxicity of bleomycin (BLM) under aerated and hy...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1978.34
更新日期:1978-02-01 00:00:00
abstract::To assess the precise role of IGF1 in benign and malignant breast diseases, we analysed the tissular localisation, characterised, and quantified specific insulin-like growth factor 1 (IGF1) binding sites in these heterogenous tissues, using histo-autoradiographic analysis (HAA). The 125I-IGF1 binding was performed on ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1992.252
更新日期:1992-08-01 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
abstract::The sera of 80 newly diagnosed lung-cancer patients have been examined for immune complexes and autoantibodies. Control subjects consisted of 20 bronchitic patients and 150 normal blood donors. Immune-complex measurements used 4 established and sensitive techniques (Raji cell assay, fluid and solid-phase C1q assays an...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.45
更新日期:1981-03-01 00:00:00
abstract::Pancreatic cancer is the fifth most common cause of cancer death. Identification of defined patient groups based on a prognostic index may improve the prediction of survival and selection of therapy. Many prognostic factors have been identified often based on retrospective, underpowered studies with unclear analyses. ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604568
更新日期:2008-09-16 00:00:00
abstract::We investigated whether cholecystectomy is associated with subsequent cancer and, if so, whether the association is likely to be causal, by undertaking a retrospective cohort study using linked medical statistics, comprising a cholecystectomy group (n=39 254) and a reference cohort admitted for a range of other medica...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6602392
更新日期:2005-04-11 00:00:00
abstract::In a previous report we suggested that the estimation of prothymosin alpha (PTA) levels in primary breast tumours might be used to identify breast cancer patients at high risk for distant metastasis (Dominguez F et al (1993) Eur J Cancer 29A: 893-897). Here the role of tumour PTA levels as predictor was investigated w...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.1999.0968
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:Gender-associated epigenetic alterations are poorly investigated in male and female familial breast cancer (fBC). MicroRNAs may contribute to the different biology in men and women particularly related to RASSF1A pathways. METHODS:Microarray technology was used to evaluate miRNA profile in 24 male and 43 fe...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2014.535
更新日期:2014-12-09 00:00:00
abstract::The relationship between oestrogen receptor (RE) content of primary breast cancer and subsequent prognosis was examined with regard to nodal status. It was found that, within a particular nodal group, patients with tumours containing fully functional RE experienced a longer disease-free interval than those with RE- di...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1981.9
更新日期:1981-01-01 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::Recent evidence has demonstrated that endothelial-to-mesenchymal transition (EndMT) may have a significant role in a number of diseases. Although EndMT has been previously studied as a critical process in heart development, it is now clear that EndMT can also occur postnatally in various pathologic settings, including...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/sj.bjc.6604662
更新日期:2008-11-04 00:00:00
abstract:BACKGROUND:The lifestyle risk factors for nasopharyngeal carcinoma (NPC) in North Africa are not known. METHODS:From 2002 to 2005, we interviewed 636 patients and 615 controls from Algeria, Morocco and Tunisia, frequency-matched by centre, age, sex, and childhood household type (urban/rural). Conditional logistic regr...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605281
更新日期:2009-10-06 00:00:00
abstract:BACKGROUND:Systemic inflammation measured by the neutrophil-to-lymphocyte ratio (NLR), leucocyte-to-lymphocyte ratio (LLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR) and CRP/albumin ratio (CRP/Alb) was shown to impact the survival prognosis in patients with extracranial solid cancer. METHO...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-01254-0
更新日期:2021-01-21 00:00:00
abstract::Even though the majority of patients with bladder malignancies initially present with low stage disease, the clinical epidemiology of these so-called superficial bladder tumours is not well known. In this paper, disease characteristics at initial presentation and during follow-up are described in 1,745 primary cases d...
journal_title:British journal of cancer
pub_type: 杂志文章,多中心研究
doi:10.1038/bjc.1993.147
更新日期:1993-04-01 00:00:00
abstract:BACKGROUND:Previous studies have reported up to 50% of ductal carcinoma in situ (DCIS), is HER2 positive, but the frequency of HER2-positive invasive breast cancer (IBC) is lower. The aim of this study is to characterise HER2 status in DCIS and assess its prognostic value. METHODS:HER2 status was evaluated in a large ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-019-0436-3
更新日期:2019-05-01 00:00:00
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
doi:10.1038/bjc.2014.346
更新日期:2014-07-15 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:BACKGROUND:MYCN amplification with subsequent MYCN protein overexpression is a powerful indicator of poor prognosis of neuroblastoma patients. Little is known regarding the prognostic significance of the homologous MYC protein expression in neuroblastoma. METHODS:Immunostaining for MYCN and MYC protein was performed o...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2015.188
更新日期:2015-06-30 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