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11.
Mylona E Alexandrou P Giannopoulou I Liapis G Sofia M Keramopoulos A Nakopoulou L 《Gynecologic oncology》2007,104(3):557-563
OBJECTIVES: Vascular endothelial growth factors A and B (VEGF-A and VEGF-B) play a major role in angiogenesis and activate VEGF receptor 1 (VEGFR-1). However, the clinicopathologic and clinical value of VEGF-B and VEGFR-1 in invasive breast carcinoma remains unclear. METHODS: We immunohistochemically examined the expression pattern of VEGF-A, VEGF-B and VEGFR-1 in 177 invasive breast carcinomas in relation to clinicopathological parameters, p53, c-erbB2 proteins expression and patients' survival. RESULTS: VEGF-A, VEGF-B and VEGFR-1 were immunodetected predominantly in the cytoplasm of the malignant cells. None of the studied markers correlated with any of the clinicopathological parameters, other than stromal VEGFR-1 which inversely correlated with PR (p=0.021). Cancerous VEGF-A and stromal VEGFR-1 were positively related to p53 (p=0.016 and p=0.033, respectively). Cancerous VEGF-B was positively associated with c-erbB-2 (p=0.045) and was found to exert an unfavorable impact on both disease-free and the overall survival of the node-positive patients (p=0.05 and p=0.029, respectively). Cancerous VEGFR-1 was recognized as being an independent poor prognostic indicator (p=0.037). CONCLUSION: These findings suggest that, while VEGF-B seems to be useful as a prognostic indicator only in node-positive patients, VEGFR-1 may be an independent poor prognosticator in patients with invasive breast carcinoma. 相似文献
12.
Anna Suchankova Margarita Stampelou Klontiana Koutsouki Athanasios Pousias Lakshiv Dhingra Kerry Barkan Nicole Pouli Panagiotis Marakos Roxane Tenta Antonios Kolocouris Nikolaos Lougiakis Graham Ladds 《ACS medicinal chemistry letters》2022,13(6):923
Here we describe the design and synthesis of pyrazolo[3,4-d]pyridazines as adenosine receptor (AR) ligands. We demonstrate that the introduction of a 3-phenyl group, together with a 7-benzylamino and 1-methyl group at the pyrazolopyridazine scaffold, generated the antagonist compound 10b, which displayed 21 nM affinity and a residence time of ∼60 min, for the human A1R, 55 nM affinity and a residence time of ∼73 min, for the human A3R and 1.7 μΜ affinity for the human A2BR while not being toxic. Strikingly, the 2-methyl analog of 10b, 15b, had no significant affinity. Docking calculations and molecular dynamics simulations of the ligands inside the orthosteric binding area suggested that the 2-methyl group in 15b hinders the formation of hydrogen bonding interactions with N6.55 which are considered critical for the stabilization inside the orthosteric binding cavity. We, therefore, demonstrate that 10a is a novel scaffold for the development of high affinity AR ligands. From the mutagenesis experiments the biggest effect was observed for the Y2717.46A mutation which caused an ∼10-fold reduction in the binding affinity of 10b. 相似文献
13.
14.
David M. Gilligan Antonios Marsonis Jayshree Joshi Stephen R. Bloom Celia M. Oakley Petros Nihoyannopoulos Mohammad A. Ghatei 《Clinical cardiology》1996,19(2):129-135
Some patients with hypertrophic cardiomyopathy experience postprandial exacerbation of symptoms. The aim of this study was to determine whether the hemodynamic and/or hormonal responses to a meal differ between patients with and without postprandial symptoms. Ten hypertrophic cardiomyopathy patients with postprandial symptoms, 10 patients without postprandial symptoms, and 10 normal subjects ate a 740 Kcal meal, following which heart rate, blood pressure, and echocardiographic and gastrointestinal hormone changes were compared among the three groups. Heart rate increased (p<0.001) and diastolic blood pressure fell (p < 0.001) to a similar degree in the three groups. Left ventricular outflow tract velocity increased (p< 0.01) and some patients had substantial increases in outflow tract pressure gradient; however, this was independent of the presence or absence of postprandial symptoms. The atrial contribution to filling increased in normal subjects and in both groups of hypertrophic cardiomyopathy patients. There was no significant difference in the gastrointestinal hormone changes in the three groups. In summary, there is no evidence for a distinctive hemodynamic or hormonal response to food in hypertrophic cardiomyopathy patients with postprandial symptoms. These symptoms more likely reflect differences in underlying cardiac disease characteristics and severity. 相似文献
15.
Karim Abou-Elenin Antonios Xydakis Osama Hamdy Panayiotis A Economides Edward S Horton Aristidis Veves 《Microvascular research》2002,63(1):91-95
The two main objectives of this study were: (1) to examine the effect of aspirin on the endothelial function in healthy subjects and (2) to examine the effect of deionized water and 5% NaCl as iontophoresis solution vehicles. The skin microcirculation was evaluated at the forearm level of healthy subjects. A laser Doppler scanner was employed to measure vasodilation in response to the iontophoresis of 1% acetylcholine (endothelium-dependent) and 1% sodium nitroprusside (endothelium-independent). In the first experiment, nine healthy subjects were given 500 mg aspirin daily for 3 days. The microvascular reactivity was measured at the beginning and the end of the study. In the second experiment, the response to iontophoresis of acetylcholine and sodium nitroprusside as 1% solutions of deionized water was compared to the responses that were achieved after the iontophoresis of deionized water or 5% NaCl solution. After 3 days of aspirin intake, there were no changes in the vasodilatory response to acetylcholine (endothelium-dependent vasodilation) [81 +/- 11 vs 77 +/- 10 (% of increase over baseline at the beginning vs the end of the study, mean +/- SE), P = NS] or sodium nitroprusside (endothelium-independent vasodilation) (69 +/- 8 vs 64 +/- 12, P = NS). There was also a negligible response after the iontophoresis of 5% NaCl (3 +/- 4) and deionized water (6 +/- 4) in anodal mode (the mode employed for the iontophoresis of acetylcholine). In cathodal mode, employed for the iontophoresis of sodium nitroprusside, the response to 5% NaCl was still negligible but a considerable response was found after the iontophoresis of deionized water. In normal healthy subjects, aspirin administration has no effect on forearm skin microvascular reactivity, including both endothelium-dependent and endothelium-independent vasodilation. In addition, a NaCl solution would be preferable to deionized water as the iontophoresis solution vehicle. 相似文献
16.
Antonios Vitalis Alena Shantsila Gregory Y.H. Lip 《The American journal of medicine》2021,134(5):e354-e355
17.
Koutroubakis IE Petinaki E Dimoulios P Vardas E Roussomoustakaki M Maniatis AN Kouroumalis EA 《International journal of colorectal disease》2003,18(3):254-259
BACKGROUND AND AIMS: Initiation of a fibrotic process has been suggested as part of the intestinal response to chronic inflammation in inflammatory bowel disease. YKL-40 has been proposed as a new serum marker of fibrosis. We studied compared the serum levels of YKL-40 in patients with ulcerative colitis or Crohn's disease with inflammatory and healthy controls. PATIENTS AND METHODS: YKL-40 serum levels were measured in 179 patients with inflammatory bowel disease (94 ulcerative colitis, 85 Crohn's disease), in 23 with intestinal inflammation of other causes, and 70 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. YKL-40 levels were assessed in terms of disease activity, type and localization. RESULTS: Mean serum YKL-40 levels were 102.6+/-82.7 ng/ml in ulcerative colitis patients and 112.2+/-83.7 ng/ml in Crohn's disease patients, significantly higher than in healthy controls (64.1+/-21.4 ng/ml) but not significantly different from inflammatory controls (77.8+/-23.1 ng/ml). Disease activity and C-reactive protein levels were significantly correlated with YKL-40 levels in both ulcerative colitis and Crohn's disease. Crohn's disease patients with ileum localization had significantly higher YKL-40 levels than those with ileocolonic or colonic disease. Patients with stenotic disease had mean YKL-40 levels not significantly different than those with nonstenotic disease. CONCLUSION: Serum levels of YKL-40 are increased in patients with inflammatory bowel disease, and this is associated with the inflammatory process rather than with the degree of fibrosis. 相似文献
18.
Salamé E Osta H Antonios S Abdel-Massih T Gerbaka B Kassab R 《Annales de cardiologie et d'angeiologie》2005,54(5):292-295
Chaotic atrial tachycardia is a rare arrhythmia that has no known etiology and that usually inflicts upon newborn infants. The diagnosis is established using the surface electrocardiogram (ECG) which shows a spectacular polymorphism and irregularity of the atrial electrical activity. Clinical tolerability is variable depending on the ventricular rhythm. Cases that are not well tolerated and cases who do not recover spontaneously require medical treatment which relies mainly on amiodarone and other class IC anti-arrhythmic drugs. There is usually complete recovery during the first few months of life. The authors present the case of a female patient who was diagnosed with chaotic atrial tachycardia with induced cardiomyopathy following birth. She was successfully treated with amiodarone but had several relapses of the arrhythmia upon discontinuation of the drug. Although this observation is classic in its presentation, we consider that it is useful to remember this rare and frequently forgotten syndrome and to report the unique and particular aspects of our case and its evolution. 相似文献
19.
Elefsiniotis IS Pantazis KD Ilias A Pallis L Mariolis A Glynou I Kada H Moulakakis A 《European journal of gastroenterology & hepatology》2004,16(6):593-598
OBJECTIVE: Tamoxifen induced hepatotoxicity has not been investigated in breast cancer patients with pre-existing liver steatosis. The aim of our study was to investigate the most common predisposing factors for non-alcoholic fatty liver disease in breast cancer patients with liver steatosis, treated with adjuvant tamoxifen therapy, in order to evaluate their role in the appearance of tamoxifen induced hepatotoxicity. METHODS: Clinical and laboratory evaluation, including an oral glucose tolerance test, was done in 60 women with breast cancer and liver steatosis before the beginning of adjuvant tamoxifen treatment and every 6 months during treatment. Tamoxifen induced hepatotoxicity was defined as abnormal liver function tests during tamoxifen treatment whereas these test results were below the normal range at baseline control. Statistical evaluation of data was performed using parametric methodology (the chi-squared test, and Student's t-test, P < 0.05). RESULTS: Twenty-six patients (43.3%) exhibited tamoxifen induced hepatotoxicity (group A) whereas 34 (56.7%) did not (group B). The mean overall follow-up period for the whole group was 37.5 months (SD 27.8, range 6-120 months) and did not differ between the two groups (P = 0.055). There was significant statistical difference in body mass index (BMI) and baseline fasting glucose, cholesterol and triglyceride levels between the two groups. Eighteen of 26 patients (69.2%) from group A had impaired glucose tolerance compared with only 8/34 patients (23.5%) from group B (P < 0.001), a finding observed even in BMI matched patients from the two groups (62.5% vs 12.5%, P = 0.002). CONCLUSIONS: Tamoxifen induced hepatotoxicity is observed in a great proportion of breast cancer patients with pre-existing liver steatosis, especially those with higher BMI and higher glucose and lipid levels at baseline control. Glucose intolerance before the beginning of tamoxifen treatment seems to be a predictor of the hepatotoxicity, unrelated to baseline BMI. 相似文献
20.
Homouz D Perham M Samiotakis A Cheung MS Wittung-Stafshede P 《Proceedings of the National Academy of Sciences of the United States of America》2008,105(33):11754-11759
How the crowded environment inside cells affects the structures of proteins with aspherical shapes is a vital question because many proteins and protein–protein complexes in vivo adopt anisotropic shapes. Here we address this question by combining computational and experimental studies of a football-shaped protein (i.e., Borrelia burgdorferi VlsE) in crowded, cell-like conditions. The results show that macromolecular crowding affects protein-folding dynamics as well as overall protein shape. In crowded milieus, distinct conformational changes in VlsE are accompanied by secondary structure alterations that lead to exposure of a hidden antigenic region. Our work demonstrates the malleability of “native” proteins and implies that crowding-induced shape changes may be important for protein function and malfunction in vivo. 相似文献