49 research outputs found
Geological and historical findings reveal differential anthropogenic substrate control in unique streets of Diemen, The Netherlands
Cell-free DNA mutations as biomarkers in breast cancer patients receiving tamoxifen
The aim was to identify mutations in serum cell-free DNA (cfDNA) associated with disease progression on tamoxifen treatment in metastatic breast cancer (MBC). Sera available at start of therapy, during therapy and at disease progression were selected from 10 estrogen receptor (ER)-positive breast cancer patients. DNA from primary tumor and normal tissue and cfDNA from minute amounts of sera were analyzed by targeted next generation sequencing (NGS) of 45 genes (1,242 exons). At disease progression, stop-gain single nucleotide variants (SNVs) for CREBBP (1 patient) and SMAD4 (1 patient) and non-synonymous SNVs for AKAP9 (1 patient), PIK3CA (2 patients) and TP53 (2 patients) were found. Mutations in CREBBP and SMAD4 have only been occasionally reported in breast cancer. All mutations, except for AKAP9, were also present in the primary tumor but not detected in all blood specimens preceding progression. More sensitive detection by deeper re-sequencing and digital PCR confirmed the occurrence of circulating tumor DNA (ctDNA) and these biomarkers in blood specimens
Cell-free DNA mutations as biomarkers in breast cancer patients receiving tamoxifen
The aim was to identify mutations in serum cell-free DNA (cfDNA) associated with disease progression on tamoxifen treatment in metastatic breast cancer (MBC). Sera available at start of therapy, during therapy and at disease progression were selected from 10 estrogen receptor (ER)-positive breast cancer patients. DNA from primary tumor and normal tissue and cfDNA from minute amounts of sera were analyzed by targeted next generation sequencing (NGS) of 45 genes (1,242 exons). At disease progression, stop-gain single nucleotide variants (SNVs) for CREBBP (1 patient) and SMAD4 (1 patient) and non-synonymous SNVs for AKAP9 (1 patient), PIK3CA (2 patients) and TP53 (2 patients) were found. Mutations in CREBBP and SMAD4 have only been occasionally reported in breast cancer. All mutations, except for AKAP9, were also present in the primary tumor but not detected in all blood specimens preceding progression. More sensitive detection by deeper re-sequencing and digital PCR confirmed the occurrence of circulating tumor DNA (ctDNA) and these biomarkers in blood specimens
Correction:Â Protocol of the Healthy Brain Study:An accessible resource for understanding the human brain and how it dynamically and individually operates in its bio-social context
[This corrects the article DOI: 10.1371/journal.pone.0260952.]
Pooled analysis of prognostic impact of urokinase-type plasminogen activator and its inhibitor PAI-1 in 8377 breast cancer patients
BACKGROUND: Urokinase-type plasminogen activator (uPA) and its inhibitor
(PAI-1) play essential roles in tumor invasion and metastasis. High levels
of both uPA and PAI-1 are associated with poor prognosis in breast cancer
patients. To confirm the prognostic value of uPA and PAI-1 in primary
breast cancer, we reanalyzed individual patient data provided by members
of the European Organization for Research and Treatment of Cancer-Receptor
and Biomarker Group (EORTC-RBG). METHODS: The study included 18 datasets
involving 8377 breast cancer patients. During follow-up (median 79
months), 35% of the patients relapsed and 27% died. Levels of uPA and
PAI-1 in tumor tissue extracts were determined by different immunoassays;
values were ranked within each dataset and divided by the number of
patients in that dataset to produce fractional ranks that could be
compared directly across datasets. Associations of ranks of uPA and PAI-1
levels with relapse-free survival (RFS) and overall survival (OS) were
analyzed by Cox multivariable regression analysis stratified by dataset,
including the following traditional prognostic variables: age, menopausal
status, lymph node status, tumor size, histologic grade, and steroid
hormone-receptor status. All P values were two-sided. RESULTS: Apart from
lymph node status, high levels of uPA and PAI-1 were the strongest
predictors of both poor RFS and poor OS in the analyses of all patients.
Moreover, in both lymph node-positive and lymph node-negative patients,
higher uPA and PAI-1 values were independently associated with poor RFS
and poor OS. For (untreated) lymph node-negative patients in particular,
uPA and PAI-1 included together showed strong prognostic ability (all
P<.001). CONCLUSIONS: This pooled analysis of the EORTC-RBG datasets
confirmed the strong and independent prognostic value of uPA and PAI-1 in
primary breast cancer. For patients with lymph node-negative breast
cancer, uPA and PAI-1 measurements in primary tumors may be especially
useful for designing individualized treatment strategies
Pooled Analysis of Prognostic Impact of Urokinase-Type Plasminogen Activator and Its Inhibitor PAI-1 in 8377 Breast Cancer Patients
Background: Urokinase-type plasminogen activator (uPA) and its inhibitor (PAI-1) play essential roles in tumor invasion and metastasis. High levels of both uPA and PAI-1 are associated with poor prognosis in breast cancer patients. To confirm the prognostic value of uPA and PAI-1 in primary breast cancer, we reanalyzed individual patient data provided by members of the European Organization for Research and Treatment of Cancer-Receptor and Biomarker Group (EORTC-RBG). Methods: The study included 18 datasets involving 8377 breast cancer patients. During follow-up (median 79 months), 35% of the patients relapsed and 27% died. Levels of uPA and PAI-1 in tumor tissue extracts were determined by different immunoassays; values were ranked within each dataset and divided by the number of patients in that dataset to produce fractional ranks that could be compared directly across datasets. Associations of ranks of uPA and PAI-1 levels with relapse-free survival (RFS) and overall survival (OS) were analyzed by Cox multivariable regression analysis stratified by dataset, including the following traditional prognostic variables: age, menopausal status, lymph node status, tumor size, histologic grade, and steroid hormone-receptor status. All P values were two-sided. Results: Apart from lymph node status, high levels of uPA and PAI-1 were the strongest predictors of both poor RFS and poor OS in the analyses of all patients. Moreover, in both lymph node-positive and lymph node-negative patients, higher uPA and PAI-1 values were independently associated with poor RFS and poor OS. For (untreated) lymph node-negative patients in particular, uPA and PAI-1 included together showed strong prognostic ability (all P<.001). Conclusions: This pooled analysis of the EORTC-RBG datasets confirmed the strong and independent prognostic value of uPA and PAI-1 in primary breast cancer. For patients with lymph node-negative breast cancer, uPA and PAI-1 measurements in primary tumors may be especially useful for designing individualized treatment strategie