Abstract:
:Cardiotoxicity is the main dose-limiting side effect of doxorubicin in the clinic. Being a free radical producer, doxorubicin affects the heart specifically because of its low antioxidant capacity. Among those antioxidants, catalase is present in very low levels in the heart compared to other organs. Since catalase is an essential enzyme in detoxifying hydrogen peroxide, the aim of the present study was to investigate the protective effect of catalase as delivered by an adenovirus vector against doxorubicin-induced cardiotoxicity in cultured neonatal rat cardiac myocytes (NeRCaMs). 7-Monohydroxyethylrutoside (MonoHER), a potent cardioprotector currently under clinical investigations, was included in the study as a reference. Neonatal rat cardiac myocytes were infected with different multiplicity of infections (MOIs) of adenovirus encoding catalase (AdCat). A control infection with an adenovirus vector encoding a nonrelated protein was included. The activity and content of catalase in infected cells were determined during 3 days postinfection. One group of NeRCaMs was infected with AdCat before treatment with doxorubicin (0-50 microM). The second and third group were treated with doxorubicin (0-50 microM) with and without 1 mM monohydroxyethylrutoside (monoHER), respectively. The LDH release and viability of treated cells were measured 24 and 48 h after doxorubicin treatment. The beating rate was followed in three other groups of cells receiving the same treatments within 3 days after doxorubicin (0-100 microM) treatment. Catalase activity increased in AdCat-infected cells, with different MOIs, starting from the second day after infection as compared to the mock-infected cells (P<0.03). At the third day of infection, an MOI of more than 50 caused cytopathic effects, which hampered the use of higher viral titres. With an MOI of 50, catalase activity increased 3.5-fold in AdCat-infected cells 3 days postinfection (P=0.021) compared to mock-infected cells. The beating rate and survival of NeRCaMs decreased in a concentration and time-dependent manner after doxorubicin treatment (P<0.0005). This cytotoxicity was associated with an increase in the LDH release from the treated cells (P<0.0005). The cells stopped beating 24 h after treatment with >50 microM doxorubicin. A 3.5-fold increase in the activity of catalase did not protect NeRCaMs against any of the cytotoxic effects of doxorubicin on NeRCaMs. In contrast, monoHER (1 mM) significantly protected NeRCaMs against the lethal effects of doxorubicin on the survival, LDH release and the beating rate of NeRCaMs (P<0.004) during 48 h after doxorubicin treatment. This protection resulted in a prolongation of the beating of doxorubicin-treated cells after the end of the experiment (i.e. >72 h). The present study (1) illustrates that the cytotoxicity of high MOI of AdCat (>50) limited the possibility to increase catalase activity more than 3.5-fold, which was not enough to protect infected NeRCaMs against doxorubicin-induced cardiotoxicity and (2) confirms the efficacy of monoHER as a cardioprotector. Thus, the use of monoHER proves more suitable for the prevention of doxorubicin-induced cardiotoxicity than catalase gene transfer employing adenovirus vectors.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Abou-El-Hassan MA,Rabelink MJ,van der Vijgh WJ,Bast A,Hoeben RCdoi
10.1038/sj.bjc.6601430subject
Has Abstractpub_date
2003-12-01 00:00:00pages
2140-6issue
11eissn
0007-0920issn
1532-1827pii
6601430journal_volume
89pub_type
杂志文章abstract::Clinical data were reviewed in 325 patients with prostatic adenocarcinoma followed up for a mean of 13 years. Paraffin-embedded tumour biopsy specimens from the primary tumours were available for flow cytometry (FCM) in 273 cases. Intra-tumour heterogeneity in DNA index (DI) was found in 4% of the tumours (54 cases we...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1994.298
更新日期:1994-08-01 00:00:00
abstract::Gain of 1q is one of the most common alterations in cancer and has been associated with adverse clinical behaviour in ependymoma. The aim of this study was to investigate this region to gain insight into the role of 1q genes in intracranial paediatric ependymoma. To address this issue we generated profiles of eleven e...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604651
更新日期:2008-10-07 00:00:00
abstract::New therapeutic strategies are now being developed against adenocarcinoma associated with erbB-2 amplification, particularly by inhibiting p185erbB-2 expression. Antisense oligodeoxynucleotides seem promising for this purpose as long as they are efficiently protected against degradation and targeted into the cells. We...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1998.238
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND:Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumour and has poor prognosis. Currently, systematic chemotherapy is the only approach to prolong survival. Thus the development of new treatment regimens is urgently needed to improve the therapeutic efficacy. Our study intended to ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.55
更新日期:2017-04-11 00:00:00
abstract:BACKGROUND:Several microRNA (miRNA) molecules have emerged as important post-transcriptional regulators of tumour suppressor and oncogene expression. Ras association domain family member 1 (RASSF1) is a critical tumour suppressor that controls multiple aspects of cell proliferation such as cell cycle, cell division and...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.110
更新日期:2017-05-23 00:00:00
abstract::Electron spin resonance (ESR) spectroscopy was used to examine changes in the concentration of paramagnetic metal ions in Yoshida tumours carried by female Wistar rats. Blood, spleen and lymph nodes from these animals were also examined by ESR. A decrease in the concentration of a paramagnetic species associated with ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1976.211
更新日期:1976-11-01 00:00:00
abstract::The presence of specific and high affinity epidermal growth factor receptors (EGF-R) has been demonstrated in human prostate cancer (CaP). Scatchard analysis of the binding data revealed a linear plot consistent with a single class of binding sites with a mean dissociation constant (Kd) +/- s.d. = 1.6 +/- 0.4 nmol 1-1...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1989.216
更新日期:1989-07-01 00:00:00
abstract::Sera from breast cancer patients and from female controls were tested for inhibition of lysis of antibody-coated target cells by human leukocytes (K cells). Sera from 39% of breast cancer patients, but from only 8% of controls, inhibited lysis by more than 30%. This inhibition was unrelated to the stage of the disease...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1976.224
更新日期:1976-12-01 00:00:00
abstract:BACKGROUND:Breast cancer 1, early onset (BRCA1) is a tumour-suppressor gene associated with familial epithelial ovarian cancer (EOC). Reduced BRCA1 expression is associated with enhanced sensitivity to platinum-based chemotherapy. We sought to examine the prognostic relevance of BRCA1 expression in EOC patients treated...
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.2013.70
更新日期:2013-04-02 00:00:00
abstract:BACKGROUND:The HMGA2 protein has experimentally been linked to EMT and cancer stemness. Recent studies imply that tumour-stroma interactions regulate these features and thereby contribute to tumour aggressiveness. METHODS:We analysed 253 cases of pancreatic ductal adenocarcinoma (PDAC) and 155 cases of ampullary adeno...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2017.140
更新日期:2017-06-27 00:00:00
abstract:BACKGROUND:Elderly cancer patients form a heterogeneous population in which therapeutic decision-making is often difficult. The aim of this randomised phase II trial was to evaluate the feasibility and activity of weekly docetaxel/gemcitabine (DG) followed by erlotinib after progression (arm A) vs erlotinib followed by...
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.2011.331
更新日期:2011-10-11 00:00:00
abstract::Detailed data were provided by the Oxford Survey of Childhood Cancer OSCC on deaths from childhood cancer in Britain after irradiation of the fetus during diagnostic radiology of the mother. In each age group at death, 0-5, 6-9 and 10-15 years, excess cancer deaths decreased suddenly for births in and after 1958. A ma...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
doi:10.1038/bjc.1990.249
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND:The purpose of this study was to identify prostate cancer (PC) oncogenic microRNAs (miRs) based on miR microarray and to investigate whether these oncogenic miRs may be useful as PC biomarkers. METHODS:Initially, we carried out miR microarray and real-time PCR using RWPE-1, PC-3, DU-145 and LNCaP cells. To ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2013.125
更新日期:2013-04-30 00:00:00
abstract::Previous studies have demonstrated that BR-931, a hepatic peroxisome proliferator, can induce liver tumours in mice and rats. Since alterations in gene expression may play a critical role in multistage hepatocarcinogenesis, the present studies examined the expression of the c-myc, c-H-ras, epidermal growth factor (EGF...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1991.406
更新日期:1991-11-01 00:00:00
abstract::Cell line studies demonstrate that the PI3K/Akt pathway is upregulated in hormone-refractory prostate cancer (HRPC) and can result in phosphorylation of the androgen receptor (AR). The current study therefore aims to establish if this has relevance to the development of clinical HRPC. Immunohistochemistry was employed...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604152
更新日期:2008-03-25 00:00:00
abstract::Treatment failure in AML is often attributed to P-glycoprotein-associated multidrug resistance. However, the importance of increased DNA repair in resistant cells is becoming more apparent. In order to investigate the ability of the DNA repair inhibitor aphidicolin to modulate drug resistance, we continually exposed b...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1054/bjoc.2000.1639
更新日期:2001-03-02 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
abstract:BACKGROUND:The mitogen-activated protein kinase (MAPK) pathway has been implicated in the molecular pathogenesis of human cancers, including metastatic colorectal cancer (mCRC). This provides a rationale for the development of MAPK-targeted agents such as pimasertib. METHODS:Patients with KRAS mutant mCRC were treated...
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.2015.144
更新日期:2015-06-09 00:00:00
abstract:BACKGROUND:Enzastaurin, an oral serine-threonine kinase inhibitor, was initially developed as an ATP-competitive selective inhibitor against protein kinase Cβ. However, the mechanism by which enzastaurin contributes to tumourigenesis remains unclear. METHODS:We analysed the anti-tumour effects of enzastaurin in 22 lun...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.7
更新日期:2012-02-28 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:BACKGROUND:Consumption of wholegrain (WG) products may protect against colon and rectal cancer. METHODS:The associations between total and individual WG product consumption and colon and rectal cancer risk were prospectively examined using data on 461 incident cases of colon cancer and 283 incident cases of rectal can...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6605806
更新日期:2010-08-24 00:00:00
abstract::A phase I study of the bispecific antibody MDX-H210 in combination with granulocyte colony-stimulating factor (G-CSF) was performed in stage IV breast carcinoma patients, overexpressing HER-2/neu. MDX-H210, constructed by crosslinking antigen binding fragments (F(ab') fragments) of monoclonal antibody (mAb) H22 to Fc ...
journal_title:British journal of cancer
pub_type: 临床试验,杂志文章
doi:10.1038/sj.bjc.6601367
更新日期:2003-12-15 00:00:00
abstract:BACKGROUND:The human epidermal growth factor receptor (EGFR) is an important therapeutic target in oncology, and three different types of EGFR inhibitors have been approved for the treatment of cancer patients. However, there has been no clear association between the expression levels of EGFR protein in the tumours det...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.27
更新日期:2012-02-28 00:00:00
abstract::To evaluate whether green tea consumption provides protection against stomach cancer death, relative risks were calculated using Cox proportional hazards regression analysis in the Japan Collaborative Study for Evaluation of Cancer Risk, sponsored by the Ministry of Health and Welfare (JACC Study). The study was based...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600487
更新日期:2002-07-29 00:00:00
abstract:BACKGROUND:Overexpression of plasma membrane multi-drug resistance protein 1 (MRP-1) can lead to multidrug resistance. In this study, we describe for the first time the expression of mitochondrial MRP-1 in untreated human normal and cancer cells and tissues. METHODS:MRP-1 expression and subcellular localisation in nor...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.2012.40
更新日期:2012-03-13 00:00:00
abstract::Increasingly, reverse transcriptase polymerase chain reaction (RT-PCR) is used to detect clinically significant tumour cells in blood or bone marrow. This may result in a redefinition of disease-free and clinical relapse. However, its clinical utility may be limited by lack of automation or reproducibility. Recent stu...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6600014
更新日期:2002-01-07 00:00:00
abstract:BACKGROUND:For patients with locally advanced rectal cancer (LARC), it is unclear whether neoadjuvant chemoradiotherapy-induced pathologic complete response (pCR) individuals would further benefit from adjuvant chemotherapy (ACT). METHODS:The pCR individuals who received different ACT cycles were paired by propensity ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/s41416-020-0989-1
更新日期:2020-10-01 00:00:00
abstract::Comparison of 9 and 35 GHz spectra, obtained from frozen and lyophilized tissues, with those from model systems containing ascorbic acid, confirm that the major component of the "lyophilization signal" of tissue is the ascorbyl radical, stabilized by adsorption on an inert matrix. The magnitude of the signal under ano...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1984.10
更新日期:1984-01-01 00:00:00
abstract::The antiapoptotic Livin/ML-IAP gene has recently gained much attention as a potential new target for cancer therapy. Reports indicating that livin is expressed almost exclusively in tumours, but not in the corresponding normal tissue, suggested that the targeted inhibition of livin may present a novel tumour-specific ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/sj.bjc.6604028
更新日期:2007-11-05 00:00:00
abstract::Ultrafiltrates from spleen inhibited both DNA synthesis and the proliferation of normal lymphocytes stimulated inculture from both mouse and man without apparent cytotoxicity. However, the same doses of this spleen ultrafiltrate will kill up to two-thirds of the leukaemic lymphoblasts from both mouse and man after 24 ...
journal_title:British journal of cancer
pub_type: 杂志文章
doi:10.1038/bjc.1975.280
更新日期:1975-12-01 00:00:00