A Milk-Fat Based Diet Increases Metastasis in the MMTV-PyMT Mouse Model of Breast Cancer.

A high-fat diet (HFD) and obesity are risk factors for many diseases including breast cancer. This is particularly important with close to 40% of the current adult population being overweight or obese. Previous studies have implicated that Mediterranean diets (MDs) partially protect against breast cancer. However, to date, the links between diet and breast cancer progression are not well defined. Therefore, to begin to define and assess this, we used an isocaloric control diet (CD) and two HFDs enriched with either olive oil (OOBD, high in oleate, and unsaturated fatty acid in MDs) or a milk fat-based diet (MFBD, high in palmitate and myristate, saturated fatty acids in Western diets) in a mammary polyomavirus middle T antigen mouse model (MMTV-PyMT) of breast cancer. Our data demonstrate that neither MFBD or OOBD altered the growth of primary tumors in the MMTV-PyMT mice. The examination of lung metastases revealed that OOBD mice exhibited fewer surface nodules and smaller metastases when compared to MFBD and CD mice. These data suggest that different fatty acids found in different sources of HFDs may alter breast cancer metastasis.

Loss of sphingosine kinase 1 increases lung metastases in the MMTV-PyMT mouse model of breast cancer.

Breast cancer is a very heterogeneous disease, and ~30% of breast cancer patients succumb to metastasis, highlighting the need to understand the mechanisms of breast cancer progression in order to identify new molecular targets for treatment. Sphingosine kinase 1 (SK1) has been shown to be upregulated in patients with breast cancer, and several studies have suggested its involvement in breast cancer progression and/or metastasis, mostly based on cell studies. In this work we evaluated the role of SK1 in breast cancer development and metastasis using a transgenic breast cancer model, mouse mammary tumor virus-polyoma middle tumor-antigen (MMTV-PyMT), that closely resembles the characteristics and evolution of human breast cancer. The results show that SK1 deficiency does not alter tumor latency or growth, but significantly increases the number of metastatic lung nodules and the average metastasis size in the lung of MMTV-PyMT mice. Additionally, analysis of Kaplan-Meier plotter of human disease shows that high SK1 mRNA expression can be associated with a better prognosis for breast cancer patients. These results suggest a metastasis-suppressing function for SK1 in the MMTV-PyMT model of breast cancer, and that its role in regulating human breast cancer progression and metastasis may be dependent on the breast cancer type.

Non-invasive continuous blood pressure monitoring of tachycardic episodes during interventional electrophysiology.

AIMS: We thought to evaluate feasibility of continuous non-invasive blood pressure monitoring during procedures of interventional electrophysiology. METHODS AND RESULTS: We evaluated continuous non-invasive finger blood pressure (BP) monitoring by means of the Nexfin device in 22 patients (mean age 70 ± 24 years), undergoing procedures of interventional electrophysiology, in critical situations of hypotension caused by tachyarrhythmias or by intermittent incremental ventricular temporary pacing till to the maximum tolerated systolic BP fall (mean 61 ± 14 mmHg per patient at a rate of 195 ± 37 bpm). In all patients, Nexfin was able to detect immediately, at the onset of tachyarrythmia, the changes in BP and recorded reliable waveforms. The quality of the signal was arbitrarily classified as excellent in 11 cases, good in 10 cases, and sufficient in 1 case. In basal conditions, calibrations of the signal occurred every 49.2 ± 24.3 s and accounted for 4% of total monitoring time; during tachyarrhythmias their frequency increased to one every 12.7 s and accounted for 19% of total recording duration. A linear correlation for a range of BP values from 41 to 190 mmHg was found between non-invasive and intra-arterial BP among a total of 1055 beats from three patients who underwent simultaneous recordings with both methods (coefficient of correlation of 0.81, P < 0.0001). CONCLUSION: In conclusion, continuous non-invasive BP monitoring is feasible in the clinical practise of an interventional electrophysiology laboratory without the need of utilization of an intra-arterial BP line.