Lipids and cholesterol in particular, have long been associated with breast cancer (BC) onset and progression. However, the causative effects of elevated lipid levels and breast cancer remain largely undisclosed and were the subject of the present study.We took advantage of well-established in vitro and in vivo models of cholesterol enrichment to exploit the mechanism involved in LDL-cholesterol favouring BC growth and invasiveness. We analyzed its effects in models that mimic different BC subtypes and stages.Our data show that LDL-cholesterol (but not HDL-cholesterol) promotes BC cells proliferation, migration and loss of adhesion, hallmarks of the epithelial to mesenchymal transition. In vivo studies modeling cholesterol levels showed that breast tumors are consistently larger and more proliferative in hypercholesterolemic mice, which also have more frequently lung metastases. Microarray analysis revealed an over expression of intermediates of Akt and ERK pathways suggesting a survival response induced by LDL, confirmed by WB analyses. Gene expression analysis also evidenced an activation of ErbB2 signaling pathway and decreased expression of adhesion molecules (cadherin-related family member3, CD226, Claudin 7 and Ocludin) in the cells exposed to LDL.Together, the present work shows novel mechanistic evidence that high LDL-cholesterol levels promote BC progression. These data provide rationale for the clinical control of cholesterol levels in BC patients.
Background: Computed tomography (CT) enables quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, helping in outcome prediction. Methods: From 1 to 22 March 2020, patients with pneumonia symptoms, positive lung CT scan, and confirmed SARS-CoV-2 on reverse transcription-polymerase chain reaction (RT-PCR) were consecutively enrolled. Clinical data was collected. Outcome was defined as favourable or adverse (i.e., need for mechanical ventilation or death) and registered over a period of 10 days following CT. Volume of disease (VoD) on CT was calculated semi-automatically. Multiple linear regression was used to predict VoD by clinical/laboratory data. To predict outcome, important features were selected using a priori analysis and subsequently used to train 4 different models. Results: A total of 106 consecutive patients were enrolled (median age 63.5 years, range 26-95 years; 41/106 women, 38.7%). Median duration of symptoms and C-reactive protein (CRP) was 5 days (range 1-30) and 4.94 mg/L (range 0.1-28.3), respectively. Median VoD was 249.5 cm 3 (range 9.9-1505) and was predicted by lymphocyte percentage (p = 0.008) and CRP (p < 0.001). Important variables for outcome prediction included CRP (area under the curve [AUC] 0.77), VoD (AUC 0.75), age (AUC 0.72), lymphocyte percentage (AUC 0.70), coronary calcification (AUC 0.68), and presence of comorbidities (AUC 0.66). Support vector machine had the best performance in outcome prediction, yielding an AUC of 0.92. Conclusions: Measuring the VoD using a simple CT post-processing tool estimates SARS-CoV-2 burden. CT and clinical data together enable accurate prediction of short-term clinical outcome.
Background
To investigate whether quantitative radiomic features extracted from digital breast tomosynthesis (DBT) are associated with Ki-67 expression of breast cancer.
Materials and methods
This is a prospective ethically approved study of 70 women diagnosed with invasive breast cancer in 2018, including 40 low Ki-67 expression (Ki-67 proliferation index <14%) cases and 30 high Ki-67 expression (Ki-67 proliferation index ≥ 14%) cases. A set of 106 quantitative radiomic features, including morphological, grey/scale statistics, and texture features, were extracted from DBT images. After applying least absolute shrinkage and selection operator (LASSO) method to select the most predictive features set for the classifiers, low
versus
high Ki-67 expression was evaluated by the area under the curve (AUC) at receiver operating characteristic analysis. Correlation coefficient was calculated for the most significant features.
Results
A combination of five features yielded AUC of up to 0.698. The five most predictive features (sphericity, autocorrelation, interquartile range, robust mean absolute deviation, and short-run high grey-level emphasis) showed a statistical significance (
p
≤ 0.001) in the classification. Thirty-four features were significantly (
p
≤ 0.001) correlated with Ki-67, and five of these had a correlation coefficient of > 0.5.
Conclusion
The present study showed that quantitative radiomic imaging features of breast tumour extracted from DBT images are associated with breast cancer Ki-67 expression. Larger studies are needed in order to further evaluate these findings.
Timely detection of colorectal cancer metastases may permit improvements in their clinical management. Here, we investigated a putative role for bone marrow-derived cells in the induction of epithelial-to-mesenchymal transition (EMT) as a marker for onset of metastasis. In ectopic and orthotopic mouse models of colorectal cancer, bone marrow-derived CD11b(Itgam)
We investigated whether the internal gantry components of our computed tomography (CT) scanner contain severe acute respiratory syndrome 2 (SARS-CoV-2) ribonucleic acid (RNA), bacterial or fungal agents. From 1 to 27 March 2020, we performed 180 examinations of patients with confirmed SARS-CoV-2 infection using a dedicated CT scanner. On 27 March 2020, this CT gantry was opened and sampled in each of the following components: (a) gantry case; (b) inward airflow filter; (c) gantry motor; (d) x-ray tube; (e) outflow fan; (f) fan grid; (g) detectors; and (h) x-ray tube filter. To detect SARS-CoV-2 RNA, samples were analysed using reverse transcriptase-polymerase chain reaction (RT-PCR). To detect bacterial or fungal agents, samples have been collected using “replicate organism detection and counting” contact plates of 24 cm2, containing tryptic soy agar, and subsequently cultured. RT-PCR detected SARS-CoV-2 RNA in the inward airflow filter sample. RT-PCR of remaining gantry samples did not reveal the presence of SARS-CoV-2 RNA. Neither bacterial nor fungal agents grew in the agar-based growth medium after the incubation period. Our data showed that SARS-Cov-2 RNA can be found inside the CT gantry only in the inward airflow filter. All remaining CT gantry components were devoid of SARS-CoV-2 RNA.
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