Cancer cell growth suppressibility of ω-3 fatty acid whose carboxy group converted to ester group.

Recently, ω-3 fatty acids have been revealed to having cancer cell growth suppressibility. It is necessary to analyze the mechanism of cancer cell growth suppressibility and to impart selective cancer cell accumulation when creating anticancer drugs based on ω-3 fatty acids. Therefore, it is necessarily essential to introduce a luminescent molecule or a molecule which have a drug delivery function into ω-3 fatty acids, and the position of introduction is the ω-3 fatty acids' carboxyl group. On the other hand, whether the ω-3 fatty acids' cancer cell growth suppressibility is maintained when the ω-3 fatty acids' carboxyl groups are converted to other structures, such as ester groups, is unclear. In this work, a derivative was synthesized wherein the α-linolenic acid carboxyl group, one of the ω-3 fatty acids, was converted to an ester group and evaluated the cancer cell growth suppressibility, as well as the amount of cancer cell uptake. As a result, it was suggested that the ester group derivatives presented the same functionality as α-linolenic acid, and the ω-3 fatty acid carboxyl group is a flexible functional group, which can be structurally modified in terms of functionality to cancer cells.

Evaluation of Cancer Cell Growth Suppressibility of ω-3 Fatty Acids and Their Metabolites.

According to current research, cancer cell growth is suppressed by ω-3 fatty acids, which are essential fatty acids. On the other hand, ω-3 fatty acids are metabolized to bioactivities in vivo. A systematic evaluation of the ability of ω-3 fatty acids and their metabolites to suppress cancer cell growth has not been sufficiently conducted. Our work evaluated the effect of ω-3 fatty acids (docosahexaenoic acid, eicosapentaenoic acid), trans fatty acid, and the metabolites (Resolvin E1, Maresin 1) on cancer cell growth suppressibility. Our results suggest that there may be optimal fatty acids depending on the kind of cancer cells, the presence or absence of hydroxyl group, and the double bond structure involved.

A novel nutritional index "simplified CONUT" and the disease risk index independently stratify prognosis of elderly patients with acute myeloid leukemia.

Elderly patients aged 65 or older with acute myeloid leukemia (AML) have poor prognosis. The risk stratification based on genetic alteration has been proposed in national comprehensive cancer network (NCCN) guideline but its efficacy was not well verified especially in real world elderly patients. The nutritional status assessment using controlling nutritional status (CONUT) score is a prognostic biomarker in elderly patients with solid tumors but was not examined in elderly AML patients. We performed prospective analysis of genetic alterations of 174 patients aged 65 or older with newly diagnosed AML treated without hematopoietic stem cell transplantation (HSCT) and developed simplified CONUT (sCONUT) score by eliminating total lymphocyte count from the items to adapt AML patients. In this cohort, both the NCCN 2017 risk group and sCONUT score successfully stratified the overall survival (OS) of the elderly patients. A multivariable analysis demonstrated that adverse group in NCCN 2017 and high sCONUT score were independently associated with poor 2-year OS. Both risk stratification based on NCCN 2017 and sCONUT score predict prognosis in the elderly patients with newly diagnosed AML.

[The Optimal Start Timing of Helical Scan for Coronary CT Angiography and CT Myocardial Perfusion Scan Using 64-MDCT].

PURPOSE: Ichihara et al. (Fujita Med J 2015; 1(1): 9-14) developed a method to simultaneously obtain both coronary computed tomography (CT) angiography and CT myocardial perfusion (CTP) using 64-multi detector CT (MDCT). An input-function (time enhancement curve, TEC) of the ascending aorta (Ao) and myocardial CT density are necessary to calculate absolute myocardial blood flow (ml/g/min) using a two-compartment model. Helical scan starting timing is important to capture the peak (P) of Ao time enhancement curve (TEC). The purpose is to search the optimal timing of starting helical scan to capture the P. METHODS: We performed 14 CTPs using Definition AS+ (SIEMENS). A dynamic scan at the Ao level was started at 7 s after contrast injection and helical scan was started at various trigger on bolus tracking. Definition AS+ needs 2 s (other scanner may need 4 s) for changing from a dynamic to helical scan mode. We created TECs of pulmonary artery (PA) and Ao using the fifth function fitting. We measured the time from trigger point to the P (t200, t250, t300 and tCP). RESULTS: Mean t200, t250, t300 and tCP were 9.1±1.9, 7.9±2.0, 6.6±1.9 and 3.9±1.2 s, respectively. In additional other 16 CTP studies using the cross point method, we can capture the P in all (100%) examinations. CONCLUSION: Scan starting at the cross point is best for Definition AS+, and the Ao=300 HU may be best for other scanner that needs 4 s for changing scan mode to obtain a fine input function for calculating absolute myocardial blood flow.

Preferential Incorporation of Administered Eicosapentaenoic Acid Into Thin-Cap Atherosclerotic Plaques.

OBJECTIVE: n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on atherosclerosis. Although specific salutary actions have been reported, the detailed distribution of n-3 polyunsaturated fatty acids in plaque and their relevance in disease progression are unclear. Our aim was to assess the pharmacodynamics of EPA and DHA and their metabolites in atherosclerotic plaques. Approach and Results: Apolipoprotein E-deficient (Apoe-/-) mice were fed a Western diet supplemented with EPA (1%, w/w) or DHA (1%, w/w) for 3 weeks. Imaging mass spectrometry analyses were performed in the aortic root and arch of the Apoe-/- mice to evaluate the distribution of EPA, DHA, their metabolites and the lipids containing EPA or DHA in the plaques. Liquid chromatography-mass spectrometry and histological analysis were also performed. The intima-media thickness of atherosclerotic plaque decreased in plaques containing free EPA and EPAs attached with several lipids. EPA was distributed more densely in the thin-cap plaques than in the thick-cap plaques, while DHA was more evenly distributed. In the aortic root, the distribution of total EPA level and cholesteryl esters containing EPA followed a concentration gradient from the vascular endothelium to the media. In the aortic arch, free EPA and 12-hydroxy-EPA colocalized with M2 macrophage. CONCLUSIONS: Administered EPA tends to be incorporated from the vascular lumen side and preferentially taken into the thin-cap plaque.

Bronchodilator Inhalation During Ex Vivo Lung Perfusion Improves Posttransplant Graft Function After Warm Ischemia.

BACKGROUND: We hypothesized that an injured lung graft from donation after cardiac death donors could be reconditioned before transplantation using an ex vivo lung perfusion (EVLP) system and ventilation with high-dose short-acting ß2-adrenergic receptor agonists. METHODS: Cardiac arrest was induced in a canine model by intravenous potassium chloride injection. Lungs were randomly assigned to two groups after 150 minutes of warm ischemia: inhalation of 1,400 µg of procaterol (BETA group, n = 5) or control group receiving solvent (CON group, n = 5) during EVLP. Left lungs were transplanted after 120 minutes of EVLP. Functional variables, tissue adenosine 5'-triphosphate levels, and tissue cyclic adenosine monophosphate levels were measured 240 minutes after transplantation. RESULTS: Physiologic pulmonary function was similar at the end of EVLP in both groups. However, significantly better graft oxygenation, dynamic pulmonary compliance, and reduced pulmonary vascular resistance were observed in the BETA group than in the CON group 240 minutes after transplantation. No severe adverse effects were observed after lung transplantation in the BETA group. Lung tissue adenosine 5'-triphosphate levels and cyclic adenosine monophosphate levels were significantly higher in the BETA group than in the CON group at the end of EVLP and at 240 minutes after transplantation. CONCLUSIONS: High-dose nebulized procaterol during EVLP ameliorated lung graft dysfunction at the early posttransplantation period without severe adverse effects. These data suggest that lung reconditioning with procaterol ventilation during EVLP improves lung graft function after transplantation.