Abstract:
BACKGROUND:The likelihood of recurrence in patients with breast cancer who have HER2-positive tumors is relatively high, although trastuzumab is a remarkably effective drug in this setting. Signal transducer and activator of transcription 3 protein (STAT3), a transcription factor that is persistently tyrosine-705 phosphorylated (pSTAT3) in response to numerous oncogenic signaling pathways, activates downstream proliferative and anti-apoptotic pathways. We hypothesized that pSTAT3 expression in HER2-positive breast cancer will confer trastuzumab resistance. METHODS:We integrated reverse phase protein array (RPPA) and gene expression data from patients with HER2-positive breast cancer treated with trastuzumab in the adjuvant setting. RESULTS:We show that a pSTAT3-associated gene signature (pSTAT3-GS) is able to predict pSTAT3 status in an independent dataset (TCGA; AUC = 0.77, P = 0.02). This suggests that STAT3 induces a characteristic set of gene expression changes in HER2-positive cancers. Tumors characterized as high pSTAT3-GS were associated with trastuzumab resistance (log rank P = 0.049). These results were confirmed using data from the prospective, randomized controlled FinHer study, where the effect was especially prominent in HER2-positive estrogen receptor (ER)-negative tumors (interaction test P = 0.02). Of interest, constitutively activated pSTAT3 tumors were associated with loss of PTEN, elevated IL6, and stromal reactivation. CONCLUSIONS:This study provides compelling evidence for a link between pSTAT3 and trastuzumab resistance in HER2-positive primary breast cancers. Our results suggest that it may be valuable to add agents targeting the STAT3 pathway to trastuzumab for treatment of HER2-positive breast cancer.
journal_name
BMC Medjournal_title
BMC medicineauthors
Sonnenblick A,Brohée S,Fumagalli D,Vincent D,Venet D,Ignatiadis M,Salgado R,Van den Eynden G,Rothé F,Desmedt C,Neven P,Loibl S,Denkert C,Joensuu H,Loi S,Sirtaine N,Kellokumpu-Lehtinen PL,Piccart M,Sotiriou Cdoi
10.1186/s12916-015-0416-2subject
Has Abstractpub_date
2015-08-03 00:00:00pages
177issn
1741-7015pii
10.1186/s12916-015-0416-2journal_volume
13pub_type
杂志文章相关文献
BMC Medicine文献大全abstract::Integration of the viral genome into host cell chromatin is a pivotal and unique step in the replication cycle of retroviruses, including HIV. Inhibiting HIV replication by specifically blocking the viral integrase enzyme that mediates this step is an obvious and attractive therapeutic strategy. After concerted effort...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-10-34
更新日期:2012-04-12 00:00:00
abstract:BACKGROUND:Prescription of non-steroidal anti-inflammatory drugs (NSAIDs) should be based on the assessment of both gastrointestinal (GI) and cardiovascular (CV) risk for the individual patient. We aimed to assess the GI/CV risk profile and the pharmacological management of patients with osteoarthritis (OA) in clinical...
journal_title:BMC medicine
pub_type: 杂志文章,多中心研究
doi:10.1186/1741-7015-9-38
更新日期:2011-04-14 00:00:00
abstract::A decade ago celiac disease was considered extremely rare outside Europe and, therefore, was almost completely ignored by health care professionals. In only 10 years, key milestones have moved celiac disease from obscurity into the popular spotlight worldwide. Now we are observing another interesting phenomenon that i...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-10-13
更新日期:2012-02-07 00:00:00
abstract:BACKGROUND:The United States Preventive Services Task Force (USPSTF) recommends screening adults for depression in primary care settings when staff-assisted depression management programs are available. This recommendation, however, is based on evidence from depression management programs conducted with patients alread...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-12-13
更新日期:2014-01-28 00:00:00
abstract:BACKGROUND:Vertical and horizontal trust, as dimensions of social capital, may be important determinants of health. As mass media campaigns have been used extensively to promote healthy lifestyles and convey health-related information, high levels of individual trust in the media may facilitate the success of such camp...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/1741-7015-7-4
更新日期:2009-01-22 00:00:00
abstract::Alzheimer's disease is a devastating neurological disorder that affects more than 37 million people worldwide. The economic burden of Alzheimer's disease is massive; in the United States alone, the estimated direct and indirect annual cost of patient care is at least $100 billion. Current FDA-approved drugs for Alzhei...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-7-7
更新日期:2009-02-19 00:00:00
abstract:BACKGROUND:Pregnancy and pregnancy loss may be linked to cardiovascular disease (CVD). However, the evidence is still inconsistent, especially in East Asians, whose reproductive patterns differ importantly from those in the West. We examined the associations of pregnancy, miscarriage, induced abortion, and stillbirth w...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-017-0912-7
更新日期:2017-08-08 00:00:00
abstract:BACKGROUND:Risk stratification and management of acute myocardial infarction patients continue to be challenging despite considerable efforts made in the last decades by many clinicians and researchers. The aim of this study was to investigate the metabolomic fingerprint of acute myocardial infarction using nuclear mag...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-018-1240-2
更新日期:2019-01-07 00:00:00
abstract:BACKGROUND:Managing hearing communication for residents living with hearing loss and dementia in long-term care settings is challenging. This paper explores how care can be effective in optimising hearing communication for residents living with dementia. We argue that the underlying notion of permission or authorisatio...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-019-1286-9
更新日期:2019-03-04 00:00:00
abstract:BACKGROUND:The TransEurope FootRace 2009 (TEFR09) was one of the longest transcontinental ultramarathons with an extreme endurance physical load of running nearly 4,500 km in 64 days. The aim of this study was to assess the wide spectrum of adaptive responses in humans regarding the different tissues, organs and functi...
journal_title:BMC medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/1741-7015-10-78
更新日期:2012-07-19 00:00:00
abstract:BACKGROUND:It is critically important to conduct research on stigmatized conditions, to include marginalized groups that experience stigma, and to develop interventions to reduce stigma. However, such research is ethically challenging. Though superficial reference is frequently made to these widely acknowledged challen...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-019-1317-6
更新日期:2019-04-29 00:00:00
abstract::Proteinuria is a defining criterion for the diagnosis of pre-eclampsia. The amount of protein lost per day has been thought by some to predict both maternal and fetal outcome. The systematic review of 16 primary papers including over 6700 patients by Thangaratinam and colleagues published this month in BMC Medicine su...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-7-11
更新日期:2009-03-24 00:00:00
abstract::Due to the easier access to information, the availability of low cost technologies and the involvement of well educated, passionate patients, a group of citizen 'Health Hackers', who are building their own medical systems to help them overcome the unmet needs of their conditions, is emerging. This has recently been th...
journal_title:BMC medicine
pub_type: 社论
doi:10.1186/s12916-016-0670-y
更新日期:2016-08-17 00:00:00
abstract:BACKGROUND:Severe iodine insufficiency in pregnancy has significant consequences, but there is inadequate evidence to indicate what constitutes mild or moderate insufficiency, in terms of observed detrimental effects on pregnancy or birth outcomes. A limited number of studies have examined iodine status and birth outco...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-020-01602-0
更新日期:2020-06-11 00:00:00
abstract:BACKGROUND:We now know that depression is associated with a chronic, low-grade inflammatory response and activation of cell-mediated immunity, as well as activation of the compensatory anti-inflammatory reflex system. It is similarly accompanied by increased oxidative and nitrosative stress (O&NS), which contribute to ...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-11-200
更新日期:2013-09-12 00:00:00
abstract:BACKGROUND:The focus of this study is to identify particular microRNA (miRNA) signatures in exosomes derived from plasma of 435 human epidermal growth factor receptor 2 (HER2)-positive and triple-negative (TN) subtypes of breast cancer (BC). METHODS:First, miRNA expression profiles were determined in exosomes derived ...
journal_title:BMC medicine
pub_type: 杂志文章,多中心研究
doi:10.1186/s12916-018-1163-y
更新日期:2018-10-10 00:00:00
abstract::Wheat, once thought to be a critical ingredient in a healthy diet, has become a major threat, according to public opinion. The term non-celiac gluten sensitivity has been widely adopted to describe a clinical entity characterized by symptoms induced by gluten without the diagnostic criteria found in other gluten-relat...
journal_title:BMC medicine
pub_type: 评论,杂志文章
doi:10.1186/1741-7015-12-86
更新日期:2014-05-23 00:00:00
abstract:BACKGROUND:A beneficial effect of a high n-3 long-chain polyunsaturated fatty acid (LCPUFA) intake has been observed in heart failure patients, who are frequently insulin resistant. We investigated the potential influence of impaired glucose metabolism on the relation between dietary intake of n-3 LCPUFAs and risk of a...
journal_title:BMC medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/1741-7015-11-216
更新日期:2013-10-08 00:00:00
abstract::The lack of formal training programs for peer reviewers places the scientific quality of biomedical publications at risk, as the introduction of 'hidden' bias may not be easily recognized by the reader. The exponential increase in the number of manuscripts submitted for publication worldwide, estimated in the millions...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-014-0179-1
更新日期:2014-09-26 00:00:00
abstract::Malaria at international borders presents particular challenges with regards to elimination. International borders share common malaria ecologies, yet neighboring countries are often at different stages of the control-to-elimination pathway. Herein, we present a case study on malaria, and its control, at the border be...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-018-1081-z
更新日期:2018-06-26 00:00:00
abstract:BACKGROUND:All rigorous primary cardiovascular disease (CVD) prevention guidelines recommend absolute CVD risk scores to identify high- and low-risk patients, but laboratory testing can be impractical in low- and middle-income countries. The purpose of this study was to compare the ranking performance of a simple, non-...
journal_title:BMC medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/1741-7015-11-170
更新日期:2013-07-24 00:00:00
abstract:BACKGROUND:Thymic size in early infancy predicts subsequent survival in low-income settings. The human thymus develops from early gestation, is most active in early life and is highly sensitive to malnutrition. Our objective was to test whether thymic size in infancy could be increased by maternal and/or infant nutriti...
journal_title:BMC medicine
pub_type: 杂志文章,随机对照试验
doi:10.1186/s12916-019-1264-2
更新日期:2019-02-18 00:00:00
abstract::Cocaine is a stimulant that leads to the rapid accumulation of catecholamines and serotonin in the brain due to prevention of their re-uptake into the neuron that released the neurotransmitter. Cocaine dependence is a public health concern and cause of significant morbidity and mortality worldwide. At present, there a...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-9-119
更新日期:2011-11-03 00:00:00
abstract:BACKGROUND:The placebo response in patients with diabetes mellitus is very common. A systematic evaluation needs to be updated with the current evidence about the placebo response in diabetes mellitus and the associated factors in clinical trials of anti-diabetic medicine. METHODS:Literature research was conducted in ...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-020-01787-4
更新日期:2020-11-16 00:00:00
abstract:BACKGROUND:Resistance and tolerance to Plasmodium falciparum can determine the progression of malaria disease. However, quantitative evidence of tolerance is still limited. We investigated variations in the adverse impact of P. falciparum infections among African pregnant women under different intensities of malaria tr...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-017-0893-6
更新日期:2017-07-17 00:00:00
abstract:BACKGROUND:Clinical pathways are tools used to guide evidence-based healthcare that have been implemented internationally since the 1980s. However, there is widespread lack of agreement on the impact of clinical pathways on hospital resources and patient outcomes. This can be partially attributed to the confusion for b...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/1741-7015-8-31
更新日期:2010-05-27 00:00:00
abstract:BACKGROUND:Ineffective risk stratification can delay diagnosis of serious disease in patients with hematuria. We applied a systems biology approach to analyze clinical, demographic and biomarker measurements (n = 29) collected from 157 hematuric patients: 80 urothelial cancer (UC) and 77 controls with confounding patho...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/1741-7015-11-12
更新日期:2013-01-17 00:00:00
abstract:BACKGROUND:Smokers have been shown to have lower mortality after acute coronary syndrome than non-smokers. This has been attributed to the younger age, lower co-morbidity, more aggressive treatment and lower risk profile of the smoker. Some studies, however, have used multivariate analyses to show a residual survival b...
journal_title:BMC medicine
pub_type: 杂志文章,评审
doi:10.1186/1741-7015-9-97
更新日期:2011-08-23 00:00:00
abstract::Severe anemia contributes significantly to child mortality in sub-Saharan Africa. Blood transfusion is used in emergencies but carries risks. In BMC Medicine, Olupot-Olupot and colleagues report the findings of a phase II trial in children with severe anemia in Eastern Uganda. They provide important early safety and e...
journal_title:BMC medicine
pub_type: 评论,社论
doi:10.1186/1741-7015-12-68
更新日期:2014-04-25 00:00:00
abstract:BACKGROUND:Non-alcoholic fatty liver disease (NAFLD) is caused by abnormal accumulation of lipids within liver cells. Its prevalence is increasing in developed countries in association with obesity, and it represents a risk factor for non-alcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. Since N...
journal_title:BMC medicine
pub_type: 杂志文章
doi:10.1186/s12916-014-0137-y
更新日期:2014-08-26 00:00:00