scholarly journals Phased-array combination of 2D MRS for lipid composition quantification in patients with breast cancer

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Vasiliki Mallikourti ◽  
Sai Man Cheung ◽  
Tanja Gagliardi ◽  
Nicholas Senn ◽  
Yazan Masannat ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Composition ◽  
Optimal Algorithm ◽  
Signal To Noise Ratio ◽  
Breast Tumour ◽  
Correlation Spectroscopy ◽  
Acquisition Time ◽  
Double Quantum ◽  
Internal Reference

AbstractLipid composition in breast cancer, a central marker of disease progression, can be non-invasively quantified using 2D MRS method of double quantum filtered correlation spectroscopy (DQF-COSY). The low signal to noise ratio (SNR), arising from signal retention of only 25% and depleted lipids within tumour, demands improvement approaches beyond signal averaging for clinically viable applications. We therefore adapted and examined combination algorithms, designed for 1D MRS, for 2D MRS with both internal and external references. Lipid composition spectra were acquired from 17 breast tumour specimens, 15 healthy female volunteers and 25 patients with breast cancer on a clinical 3 T MRI scanner. Whitened singular value decomposition (WSVD) with internal reference yielded maximal SNR with an improvement of 53.3% (40.3–106.9%) in specimens, 84.4 ± 40.6% in volunteers, 96.9 ± 54.2% in peritumoural adipose tissue and 52.4% (25.1–108.0%) in tumours in vivo. Non-uniformity, as variance of improvement across peaks, was low at 21.1% (13.7–28.1%) in specimens, 5.5% (4.2–7.2%) in volunteers, 6.1% (5.0–9.0%) in peritumoural tissue, and 20.7% (17.4–31.7%) in tumours in vivo. The bias (slope) in improvement ranged from − 1.08 to 0.21%/ppm along the diagonal directions. WSVD is therefore the optimal algorithm for lipid composition spectra with highest SNR uniformly across peaks, reducing acquisition time by up to 70% in patients, enabling clinical applications.

scholarly journals The spectraplakin Dystonin antagonizes YAP activity and suppresses tumourigenesis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Praachi B. Jain ◽  
Patrícia S. Guerreiro ◽  
Sara Canato ◽  
Florence Janody
Keyword(s):  
Breast Cancer ◽  
Breast Tumour ◽  
Tissue Growth ◽  
Tumour Suppressor ◽  
Aberrant Expression ◽  
Breast Epithelial Cells ◽  
Mcf10a Cells ◽  
Resistance To Doxorubicin ◽  
Candidate Tumour Suppressor

AbstractAberrant expression of the Spectraplakin Dystonin (DST) has been observed in various cancers, including those of the breast. However, little is known about its role in carcinogenesis. In this report, we demonstrate that Dystonin is a candidate tumour suppressor in breast cancer and provide an underlying molecular mechanism. We show that in MCF10A cells, Dystonin is necessary to restrain cell growth, anchorage-independent growth, self-renewal properties and resistance to doxorubicin. Strikingly, while Dystonin maintains focal adhesion integrity, promotes cell spreading and cell-substratum adhesion, it prevents Zyxin accumulation, stabilizes LATS and restricts YAP activation. Moreover, treating DST-depleted MCF10A cells with the YAP inhibitor Verteporfin prevents their growth. In vivo, the Drosophila Dystonin Short stop also restricts tissue growth by limiting Yorkie activity. As the two Dystonin isoforms BPAG1eA and BPAG1e are necessary to inhibit the acquisition of transformed features and are both downregulated in breast tumour samples and in MCF10A cells with conditional induction of the Src proto-oncogene, they could function as the predominant Dystonin tumour suppressor variants in breast epithelial cells. Thus, their loss could deem as promising prognostic biomarkers for breast cancer.

[11C]Choline-PET imaging of breast cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1110-1110
Author(s):  
L. M. Kenny ◽  
R. C. Coombes ◽  
K. Contractor ◽  
J. Stebbing ◽  
A. Al-Nahhas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Imaging Modality ◽  
Imaging Techniques ◽  
Treatment Strategies ◽  
Breast Tumour ◽  
Response To Treatment ◽  
Choline Uptake ◽  
Choline Pet ◽  
Arterial Plasma

1110 Background: Molecular imaging techniques are increasingly being used in cancer diagnosis, staging, and assessment of response to treatment. This study sought to evaluate, for the first time, [11C]choline-PET in patients with breast cancer. The potential of [11C]choline-PET for differentiating tumours from normal tissue, correlation with molecular markers, determine its normal variability range, and finally the effect of trastuzumab on [11C]choline uptake in patients with breast cancer was investigated. Methods: 21 patients with newly diagnosed and recurrent breast cancer AJCC stage II-IV were enrolled in the study, all of whom had a baseline dynamic [11C]choline-PET scan with arterial sampling. 14 patients had 2 [11C]choline-PET scans to examine reproducibility, and 7 had a scan after trastuzumab. Analysis of [11C]choline uptake was measured using SUV, Ki (irreversible retention), and IRF@60min (retention using spectral analysis). Results: Breast tumour lesions were visualised by [11C]choline PET in all patients. The difference in tumour and non-tumour uptake were significant for SUV, Ki, and IRF@60 min (Wilcoxon p < 0.0001 for all parameters). [11C]choline uptake was reproducible in breast tumour lesions (r2 = 0.945 for SUV, 0.894 for Ki, and 0.799 for IRF60). The metabolism analysis of arterial plasma samples in 19 patients showed that [11C]choline decreased rapidly post-injection such that at 60 mins the mean radioactivity in arterial plasma due to choline was 15.15 ± 2.16%.Early responses to trastuzumab were determined to be significant in 5 lesions which corresponded with 3 clinical responses. Conclusions: [11C]choline-PET is a promising imaging modality in breast cancer, and could play an important role for determining response to novel treatment strategies in vivo. No significant financial relationships to disclose.

NIR Spectroscopic Detection of Breast Cancer

2005 ◽  
Vol 4 (5) ◽  
pp. 497-512 ◽  
Author(s):  
S. Nioka ◽  
B. Chance
Keyword(s):  
Breast Cancer ◽  
Blood Volume ◽  
Near Infrared ◽  
Tumor Tissue ◽  
Signal To Noise Ratio ◽  
Mirror Image ◽  
Physiological Data ◽  
Cancer Therapies ◽  
Image Position

Near infrared spectroscopy (NIRS) utilizes intrinsic optical absorption signals of blood, water, and lipid concentration available in the NIR window (600–1000 nm) as well as a developing array of extrinsic organic compounds to detect and localize cancer. This paper reviews optical cancer detection made possible through high tumor-tissue signal-to-noise ratio (SNR) and providing biochemical and physiological data in addition to those obtained via other methods. NIRS detects cancers in vivo through a combination of blood volume and oxygenation from measurements of oxy- and deoxy-hemoglobin giving signals of tumor angiogenesis and hypermetabolism. The Chance lab tends towards CW breast cancer systems using manually scannable detectors with calibrated low pressure tissue contact. These systems calculate angiogenesis and hypermetabolism by using a pair of wavelengths and referencing the mirror image position of the contralateral breast to achieve high ROC/AUC. Time domain and frequency domain spectroscopy were also used to study similar intrinsic breast tumor characteristics such as high blood volume. Other NIRS metrics are water-fat ratio and the optical scattering coefficient. An extrinsic FDA approved dye, ICG, has been used to measure blood pooling with extravasation, similar to Gadolinium in MRI. A key future development in NIRS will be new Molecular Beacons targeting cancers and fluorescing in the NIR window to enhance in vivo tumor-tissue ratios and to afford biochemical specificity with the potential for effective photodynamic anti-cancer therapies.

scholarly journals Navigator-Free Submillimeter Diffusion Imaging Using Multishot-Encoded Simultaneous Multi-Slice (MUSIUM)

2020 ◽  
Author(s):  
Wei-Tang Chang ◽  
Khoi Huynh ◽  
Pew-Thian Yap ◽  
Weili Lin
Keyword(s):  
Signal To Noise Ratio ◽  
Diffusion Imaging ◽  
Brain Structures ◽  
Peak Amplitude ◽  
Acquisition Time ◽  
Rf Power ◽  
Isotropic Resolution ◽  
Low Snr ◽  
Scan Time

Abstract The ability to achieve submillimter isotropic resolution diffusion MR imaging (dMRI) is critically important to study fine-scale brain structures. One of the major challenges in submillimeter dMRI is the inherently low signal-to-noise ratio (SNR). While approaches capable of mitigating the low SNR have been proposed, namely simultaneous multi-slab (SMSlab) and generalized slice dithered enhanced resolution with simultaneous multislice (gSlider-SMS), limitations are associated with these approaches. The SMSlab sequences suffer from the slab boundary artifacts and require additional navigators for phase estimation. On the other hand, gSlider sequences require relatively high RF power and peak amplitude, which increase the SAR and complicate the RF excitation. In this work, we developed a navigator-free multishot-encoded simultaneous multi-slice (MUSIUM) imaging approach, achieving enhanced SNR, low RF power and peak amplitude, and being free from slab boundary artifacts. The dMRI with ultrahigh resolution (0.86 mm isotropic), whole brain coverage and ~12.5 minute acquisition time were achieved, revealing detailed structures at cortical and white matter areas. The simulated and in vivo results also demonstrated that the MUSIUM imaging was minimally affected by the motion. Taken together, the MUSIUM imaging is a promising approach to achieve submillimeter diffusion imaging on 3T scanner within clinically feasible scan time.

scholarly journals Attenuating Tumour Angiogenesis: A Preventive Role of Metformin against Breast Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Shan Gao ◽  
Jingcheng Jiang ◽  
Pan Li ◽  
Huijuan Song ◽  
Weiwei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumour Progression ◽  
Breast Tumour ◽  
Ovarian Tumour ◽  
Tumour Cells ◽  
Tumour Angiogenesis ◽  
Preventive Role ◽  
Mcf 7

Metformin is one of the most widely prescribed antidiabetics for type 2 diabetes. A critical role of metformin against tumorigenesis has recently been implicated, although several studies also reported the lack of anticancer property of the antidiabetics. Given the controversies regarding the potential role of metformin against tumour progression, the effect of metformin against breast, cervical, and ovarian tumour cell lines was examined followed byin vivoassessment of metformin on tumour growth using xenograft breast cancer models. Significant inhibitory impact of metformin was observed in MCF-7, HeLa, and SKOV-3 cells, suggesting an antiproliferative property of metformin against breast, cervical, and ovarian tumour cells, respectively, with the breast tumour cells, MCF-7, being the most responsive.In vivoassessment was subsequently carried out, where mice with breast tumours were treated with metformin (20 mg/kg body weight) or sterile PBS solution for 15 consecutive days. No inhibition of breast tumour progression was detected. However, tumour necrosis was significantly increased in the metformin-treated group, accompanied by decreased capillary formation within the tumours. Thus, despite the lack of short-term benefit of metformin against tumour progression, a preventive role of metformin against breast cancer was implicated, which is at partially attributable to the attenuation of tumour angiogenesis.

scholarly journals Inhibition of Breast Tumour Growth with Intravenously Administered PRKCA siRNA- and PTEN Tumour Suppressor Gene-Loaded Carbonate Apatite Nanoparticles

2021 ◽  
Vol 11 (17) ◽  
pp. 8133
Author(s):  
Nabilah Ibnat ◽  
Rowshan Ara Islam ◽  
Ezharul Hoque Chowdhury
Keyword(s):  
Breast Cancer ◽  
Rna Interference ◽  
Mouse Model ◽  
Cell Line ◽  
Tumour Growth ◽  
Breast Tumour ◽  
Tumour Suppressor ◽  
Carbonate Apatite ◽  
Mcf 7

Gene therapy aims to silence an oncogene through RNA interference, or replace an abnormal tumour suppressor via gene augmentation. In this study, we intended RNA interference for PRKCA oncogene and gene augmentation for PTEN tumour suppressor with a view to reduce tumour growth in a mouse model of breast cancer. Inorganic carbonate apatite nanoparticles (CA NPs) were utilized to deliver the synthetic siRNA and the purified gene-carrying plasmid DNA both in vitro and in vivo. Effects of PRKCA siRNA- and PTEN plasmid-loaded NPs on viability of MCF-7, MDA-MB-231 and 4T1 breast cancer cells were assessed by MTT assay. The cell viability data in MCF-7 cell line demonstrated that combined delivery of PRKCA specific siRNA and PTEN plasmid with CA NPs had an additive effect to significantly decrease cellular growth compared to individual treatments. In addition, we observed a similar pattern of cumulative influence for combined treatment in triple negative MDA-MB-231 breast cancer cell line. Upon treatment with PRKCA siRNA+PTEN plasmid-loaded NPs, a remarkable decrease in the phosphorylated form of AKT protein of PI3K/AKT pathway was observed in Western blot, indicative of diminished proliferative signal. Moreover, in vivo study in MCF-7 xenograft breast cancer mouse model demonstrated that the rate of growth and final tumour volume were reduced significantly in the mouse group that received intravenous treatment of PRKCA siRNA+NPs, and PTEN plasmid+NPs. Our findings demonstrated that PRKCA siRNA and PTEN plasmid loaded into CA NPs attenuated breast tumour growth, suggesting their therapeutic potential in the treatment of breast cancer.

Trans-study projection of genomic biomarkers in analysis of oncogene deregulation and breast cancer

2018 ◽  
Author(s):  
Dan Merl ◽  
Joseph Lucas ◽  
Joseph Nevins ◽  
Haige Shen ◽  
Mike West
Keyword(s):  
Breast Cancer ◽  
Breast Tumour ◽  
Biological Evaluation ◽  
Tissue Samples ◽  
Pathway Activity ◽  
Genomic Biomarkers ◽  
Human Cancers ◽  
Pathway Deregulation

This article focuses on the use of Bayesian concepts and methods in the trans-study projection of genomic biomarkers for the analysis of oncogene deregulation in breast cancer. The objective of the study is to determine the extent to which patterns of gene expression associated with experimentally induced oncogene pathway deregulation can be used to investigate oncogene pathway activity in real human cancers. This is often referred to as the in vitro to in vivo translation problem, which is addressed using Bayesian sparse factor regression analysis for model-based translation and refinement of in vitro generated signatures of oncogene pathway activity into the domain of human breast tumour tissue samples. The article first provides an overview of the role of oncogene pathway deregulation in human cancers before discussing the details of modelling and data analysis. It then considers the findings based on biological evaluation and Bayesian pathway annotation analysis.

scholarly journals Lysine demethylase 2A expression in cancer-associated fibroblasts promotes breast tumour growth

2020 ◽  
Author(s):  
Jing-Yi Chen ◽  
Chien-Feng Li ◽  
You-Syuan Lai ◽  
Wen-Chun Hung
Keyword(s):  
Breast Cancer ◽  
Transcriptional Activation ◽  
Tumour Growth ◽  
Breast Tumour ◽  
Cancer Associated Fibroblasts ◽  
Cancer Cell Proliferation ◽  
Breast Cancer Patients ◽  
Programmed Death ◽  
Lysine Demethylase

Abstract Background Our previous study demonstrated that lysine demethylase 2A (KDM2A) enhances stemness in breast cancer cells. This demethylase is also highly expressed in cancer-associated fibroblasts (CAFs). However, its clinical significance is unclear. Methods The expression of KDM2A in CAFs was studied using immunohistochemical staining and its association with clinicopathological features and patient’s survival was tested. Overexpression and knockdown strategies were used to investigate KDM2A-regulated genes in fibroblasts. Senescent cells were detected by using β-galactosidase staining. The in vivo tumour-promoting activity of stromal KDM2A was confirmed by animal study. Results Increase of stromal KDM2A is associated with advanced tumour stage and poor clinical outcome in breast cancer patients. Cancer-derived cytokines stimulated KDM2A expression in normal fibroblasts and transformed them into CAFs. Upregulation of KDM2A induced p53-dependent senescence in fibroblasts and enhanced the release of cytokines, which reciprocally promoted cancer cell proliferation. Additionally, KDM2A upregulated programmed death-ligand 1 (PD-L1) expression via transcriptional activation in fibroblasts. Knockdown of KDM2A completely abolished the tumour-promoting activity of CAFs on breast tumour growth in vivo and diminished PD-L1 expression in the stroma of tumour tissues. Conclusions Stromal KDM2A plays an oncogenic role in breast cancer and inhibition of KDM2A reduces fibroblast senescence and suppresses tumour growth.

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