Liver Metastatic Colorectal Tumor Cells Change Their Phenotype During Consecutive Passages on Chick Embryo Chorioallantoic Membrane: Lessons from the Lab to the Clinic.

BACKGROUND/AIM: Colon cancer liver metastases with desmoplastic growth pattern (dGP) have a highly heterogeneous therapy response. The aim of the study was to evaluate the dGP liver metastasis molecular profile from a chemo-naive patient by mimicking metastatic process on an experimental chick embryo chorioallantoic membrane (CAM) model. MATERIALS AND METHODS: Three successive CAM passages of dGP human colorectal liver metastases were immunophenotyped for keratin (K) 8, and 20, CLIC1, VEGF, EGFR, CD34, podoplanin, Ki67, E-cadherin and vimentin. RESULTS: Metastatic cells gradually lost K20 while K8, E-cadherin and vimentin heterogeneously increased during passages. VEGF, CLIC 1, EGFR expression increased in metastatic cells especially at the tumor graft periphery. Scattered proliferating and non-proliferating podoplanin-positive tumor cells, lymphatic and blood vessels were heterogeneously detected in tumor xenografts depending on passage stage. CONCLUSION: By mimicking repetitive metastatic processes we proved that metastatic cells change their phenotype. This may explain why not all metastases have a similar response to therapy.

Improvement of Platelet Respiration by Cell-Permeable Succinate in Diabetic Patients Treated with Statins.

Diabetes mellitus (DM) is the most severe metabolic disease that reached the level of a global pandemic and is associated with high cardiovascular morbidity. Statins are the first-line lipid-lowering therapy in diabetic patients with or without a history of atherosclerotic disease. Although well tolerated, chronic treatment may result in side effects that lead to treatment interruption. Mitochondrial dysfunction has emerged as a central pathomechanism in DM- and statin-induced side effects. Assessment of mitochondrial respiration in peripheral platelets has been increasingly used as a mirror of organ mitochondrial dysfunction. The present study aimed to assess the: (i) changes in mitochondrial respiration elicited by statins in patients with type 2 DM and (ii) the effects of cell-permeable succinate (NV118) on respiratory parameters in platelets harvested from these patients. No significant changes were found in global mitochondrial respiration of intact platelets isolated from diabetic patients treated with either atorvastatin or rosuvastatin. Similarly, no significant changes in mitochondrial respiration of permeabilized platelets were found between diabetic patients treated with atorvastatin and healthy controls. Acute ex vivo administration of NV118 significantly improved respiration in isolated platelets. These results prompt further research on the role of permeable succinate as a therapeutic alternative for improving mitochondrial function in metabolic pathologies and point to the role of peripheral platelets as a potential biomarker of treatment response.

Melissa officinalis L. Aqueous Extract Exerts Antioxidant and Antiangiogenic Effects and Improves Physiological Skin Parameters.

Melissa officinalis (MO) is a medicinal plant well-known for its multiple pharmacological effects, including anti-inflammatory, anticancer and beneficial effects on skin recovery. In this context, the present study was aimed to investigate the in vitro and in vivo safety profile of an MO aqueous extract by assessing cell viability on normal (HaCaT-human keratinocytes) and tumor (A375-human melanoma) cells and its impact on physiological skin parameters by a non-invasive method. In addition, the antioxidant activity and the antiangiogenic potential of the extract were verified. A selective cytotoxic effect was noted in A375 cells, while no toxicity was noticed in healthy cells. The MO aqueous extract safety profile after topical application was investigated on SKH-1 mice, and an enhanced skin hydration and decreased erythema and transepidermal water loss levels were observed. The in ovo CAM assay, performed to investigate the potential modulating effect on the angiogenesis process and the blood vessels impact, indicated that at concentrations of 100 and 500 µg/mL, MO aqueous extract induced a reduction of thin capillaries. No signs of vascular toxicity were recorded at concentrations as high as 1000 µg/mL. The aqueous extract of MO leaves can be considered a promising candidate for skin disorders with impaired physiological skin parameters.

Arterial function in hypertensive pregnant women. Is arterial stiffness a marker for the outcomes in pregnancy?

AIMS: Hypertension (HTN) in pregnancy is a major cause of maternal, foetal and neonatal morbimortality in both developing and developed countries. Arterial stiffness is a predictor of cardiovascular events and can be assessed through augmentation index (AIx) and pulse wave velocity (PWV). This study was intended to analyse the arterial stiffness in three categories, hypertensive pregnant women vs. healthy women (both pregnant and non-pregnant). MAIN METHODS: Between 2018 and 2019, 150 women were prospectively included into three homogenous groups, of equal sizes (N = 50): pregnant women with HTN (group 1), pregnant women without HTN (group 2), and non-pregnant women (group 3). We assessed pregnant women 3 times (in all three trimesters) and six weeks postpartum, and the women from the control group once. KEY FINDINGS: Significant differences (p < 0.001) of the hemodynamic and arterial stiffness parameters and of the heart rate (HR) (p = 0.006) were observed between groups 1 and 2. Women with pregnancy-induced HTN had different values of arterial function parameters long time before the first signs of high blood pressure (BP) occurred. Also, body mass index (BMI) had a deleterious effect in all patients, but especially in pregnant HTN women. Significant differences (p < 0.001) between groups 2 and 3 were observed regarding the BP and aortic PWV (PWVao) and, as well, significant differences (p < 0.05) between BMI, aortic systolic BP (p = 0.02), brachial AIx (p = 0.01) and pulse pressure (PP) (p = 0.049) values. SIGNIFICANCE: The current study emphasizes the importance of the assessment of arterial function parameters and BMI as markers for future BP values and outcomes throughout gestation.