Comparison of false positive rates for screening breast magnetic resonance imaging (MRI) in high risk women performed on stacked versus alternating schedules

Othman, Edress; Wang, Jue; Sprague, Brian L.; Rounds, Tiffany; Ji, Yongli; Herschorn, Sally D.; Wood, Marie

doi:10.1186/s40064-015-0793-1

Cited by 20 publications

(9 citation statements)

References 33 publications

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“…Compared to gold standard and pH-sensitive gadolinium T 1 MRI contrast agents, MnO NPs have superior MRI properties. Clinically used gadolinium chelates are not pH-sensitive, and are always in an "ON" state, which highlights any well vascularized structure and can lead to false positive diagnoses in which a benign tumor can be mistaken for a malignant tumor [11][12][13]. In addition, many standard gadolinium agents such as MultiHance have low relaxivities of~4 mM -1 s -1 at 1.5T-4.7T [14]; Mn 2+ has a higher relaxivity of~7-8 mM -1 s -1 at the same field strengths [5,15,16].…”

Section: Introductionmentioning

confidence: 99%

Tuning the size and composition of manganese oxide nanoparticles through varying temperature ramp and aging time

et al. 2020

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Manganese oxide (MnO) nanoparticles (NPs) can serve as robust pH-sensitive contrast agents for magnetic resonance imaging (MRI) due to Mn 2+ release at low pH, which generates a~30 fold change in T 1 relaxivity. Strategies to control NP size, composition, and Mn 2+ dissolution rates are essential to improve diagnostic performance of pH-responsive MnO NPs. We are the first to demonstrate that MnO NP size and composition can be tuned by the temperature ramping rate and aging time used during thermal decomposition of manganese (II) acetylacetonate. Two different temperature ramping rates (10˚C/min and 20˚C/min) were applied to reach 300˚C and NPs were aged at that temperature for 5, 15, or 30 min. A faster ramping rate and shorter aging time produced the smallest NPs of~23 nm. Shorter aging times created a mixture of MnO and Mn 3 O 4 NPs, whereas longer aging times formed MnO. Our results indicate that a 20˚C/min ramp rate with an aging time of 30 min was the ideal temperature condition to form the smallest pure MnO NPs of~32 nm. However, Mn 2+ dissolution rates at low pH were unaffected by synthesis conditions. Although Mn 2+ production was high at pH 5 mimicking endosomes inside cells, minimal Mn 2+ was released at pH 6.5 and 7.4, which mimic the tumor extracellular space and blood, respectively. To further elucidate the effects of NP composition and size on Mn 2+ release and MRI contrast, the ideal MnO NP formulation (~32 nm) was compared with smaller MnO and Mn 3 O 4 NPs. Small MnO NPs produced the highest amount of Mn 2+ at acidic pH with maximum T 1 MRI signal; Mn 3 O 4 NPs generated the lowest MRI signal. MnO NPs encapsulated within poly (lactide-co-glycolide) (PLGA) retained significantly higher Mn 2+ release and MRI signal compared to PLGA Mn 3 O 4 NPs. Therefore, MnO instead of Mn 3 O 4 should be targeted intracellularly to maximize MRI contrast.

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Section: Introductionmentioning

confidence: 99%

Tuning the size and composition of manganese oxide nanoparticles through varying temperature ramp and aging time

et al. 2020

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“…Numerous blood biomarkers including CA 15.3, carcinoembryonic antigen (CEA), CA125 and imaging modalities like ultrasound, mammography, MRI, PET, and CT are routinely used to detect primary breast tumor disease and recurrence and to assess therapeutic response [44,45]. However, they are limited in their ability to differentially diagnose and risk-stratify the disease, with high rates of false positive diagnoses [46], underscoring the need for specific markers to accurately detect highly invasive and metastatic breast tumors, and to distinguish them from low-risk indolent ones. Moreover, breast tumors frequently exhibit intrinsic or acquired resistance to chemotherapy and targeted drugs [39].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Extradomain-B Fibronectin is Associated with Invasion of Breast Cancer Cells

Vaidya

Wang

Qian

et al. 2020

Cells

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Breast tumor heterogeneity is a major impediment to oncotherapy. Cancer cells undergo rapid clonal evolution, thereby acquiring significant growth and invasive advantages. The absence of specific markers of these high-risk populations precludes efficient therapeutic and diagnostic management of the disease. Given the critical function of tumor microenvironment in the oncogenic circuitry, we sought to determine the expression profile of the extracellular matrix oncoprotein, extradomain-B fibronectin (EDB-FN) in invasive breast cancer. Analyses of TCGA/GTEx databases and immunostaining of clinical samples found a significant overexpression of EDB-FN in breast tumors, which correlated with poor overall survival. Significant upregulation of EDB-FN was observed in invasive cell populations generated from relatively less invasive MCF7 and MDA-MB-468 cells by long-term TGF-β treatment and acquired chemoresistance. Treatment of the invasive cell populations with an AKT inhibitor (MK2206-HCl) reduced their invasive potential, with a concomitant decrease in their EDB-FN expression, partly through the phosphoAKT-SRp55 pathway. EDB-FN downregulation, with direct RNAi of EDB-FN or indirectly through RNAi of SRp55, also resulted in reduced motility of the invasive cell populations, validating the correlation between EDB-FN expression and invasion of breast cancer cells. These data establish EDB-FN as a promising molecular marker for non-invasive therapeutic surveillance of aggressive breast cancer.

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“…Numerous blood biomarkers including CA 15.3, carcinoembryonic antigen (CEA), CA125 and imaging modalities like ultrasound, mammography, MRI, PET, and CT are routinely used to detect primary breast tumor disease and recurrence and to assess therapeutic response (Khatcheressian et al, 2013, Bayo et al, 2018). However, they are limited in their ability to differentially diagnose and risk-stratify the disease, with high rates of false positive diagnoses (Othman et al, 2015), underscoring the need for specific markers to accurately detect highly invasive and metastatic breast tumors, and to distinguish them from low-risk indolent ones. Moreover, breast tumors frequently exhibit intrinsic or acquired resistance to chemotherapy and targeted drugs (Huang et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Extradomain-B Fibronectin is a molecular marker of invasive breast cancer cells

Vaidya

Wang

Qian

et al. 2019

Preprint

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invasiveness 28 Abbreviations 29 BCa -Breast cancer 30 EDB-FN -Extradomain-B fibronectin 31 FN1 -Fibronectin 32 MRI -Magnetic resonance imaging 33 PET -Positron-emission tomography 34 CT -Computed tomography 35 TME -Tumor microenvironment 36 ECM -Extracellular matrix 37 TGF-β -Transforming growth factor-β 38 EMT -Epithelial to mesenchymal transition 39 CEA -Carcinoembryonic antigen 40 41 42 43 44 45 46 47 48 49 50 51 Summary Statement 52 Dynamic changes in invasive properties of breast cancer cells directly influence extradomain-B 53 fibronectin levels, suggesting its potential role as a molecular marker for active surveillance and 54 therapeutic monitoring of breast cancer. 55 Abstract 56Breast tumor heterogeneity is a major impediment to oncotherapy. Tumor cells undergo rapid 57 clonal evolution, thereby acquiring significant growth and invasive advantages. The absence of 58 specific markers of these high-risk tumors precludes efficient therapeutic and diagnostic 59 management of breast cancer. Given the critical function of tumor microenvironment in the 60 oncogenic circuitry, we sought to determine the role of the extracellular matrix oncoprotein, 61 extradomain-B fibronectin (EDB-FN), as a molecular marker of aggressive cancers. High-risk 62 invasive cell lines generated from relatively less invasive MCF7 and MDA-MB-468 breast cancer 63 cells by long-term TGF-β treatment and chemoresistance demonstrated hybrid epithelial-64 mesenchymal phenotype, enhanced motility, and significantly elevated EDB-FN levels in 2D-and 65 3D-cultures. To determine if EDB-FN could serve as a therapy-predictive marker, the invasive cell 66 lines were treated with MK2206-HCl, a pan-AKT inhibitor. Phospho-AKT depletion reduced 67 EMT and invasion of the populations, with a concomitant decrease in EDB-FN expression, partly 68 through the phosphoAKT-SRp55 pathway, demonstrating that EDB-FN expression is strongly 69 associated with high-risk breast cancer. EDB-FN is a promising molecular marker for accurate 70 detection, differential diagnosis, and non-invasive therapeutic surveillance of aggressive breast 71 cancer. 72 73 74 75 76 77 78 79Breast cancer (BCa) is a devastating disease that accounts for 41,000 deaths each year in 80 the US (Siegel et al., 2018). Although the survival rate for patients with localized BCa is close to 81 99%, it declines precipitously in patients with distant metastases and drug resistance (Siegel et al., 82 2018, DeSantis et al., 2017). A major stumbling block in the clinical management of the disease 83 is tumor heterogeneity, which plays a role in the dynamic nature of BCa progression (Baird and 84 Caldas, 2013). Whole genome sequencing and profiling studies have demonstrated that breast 85 tumors of the same histological subtype exhibit distinct molecular portraits and discrete trajectories 86 in individual BCa patients at different stages (Tsang and Tse, 2019, Eliyatkin et al., 2015, Baird 87 and Caldas, 2013). Stochastic mutations, genome instability, and clonal evolution arising from 88 selective pre...

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Comparison of false positive rates for screening breast magnetic resonance imaging (MRI) in high risk women performed on stacked versus alternating schedules

Cited by 20 publications

References 33 publications

Tuning the size and composition of manganese oxide nanoparticles through varying temperature ramp and aging time

Tuning the size and composition of manganese oxide nanoparticles through varying temperature ramp and aging time

Overexpression of Extradomain-B Fibronectin is Associated with Invasion of Breast Cancer Cells

Extradomain-B Fibronectin is a molecular marker of invasive breast cancer cells

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