Mikro-RNS-expresszio vizsgalata adenoid cysticus emlo- es nyalmirigy-carcinomakban

Adenoid cystic carcinoma is a salivary gland-derived malignant tumor, but rarely it can originate from the breast, too. The salivary gland-derived form shows a very aggressive clinical outcome, while adenoid cystic carcinoma of the breast has mostly a very good prognosis. Aim: The aim of the authors was to compare the miRNA-expression profile of breast- and salivary gland-derived cases. Method: The miRNA-profiles of two salivary gland derived and two breast-derived adenoid cystic carcinoma tissues as well as one normal breast and one salivary gland tissues were analysed using the Affymetrix(R) Gene Chip. Results: The expression of some miRNAs differed in the tumor tissues compared to their controls: the let-7b was overexpressed in salivary gland-derived adenoid cystic carcinoma, while decreased in breast-derived adenoid cystic carcinoma. In addition, the miR-24 was decreased in salivary gland-derived but overexpressed in breast-derived adenoid cystic carcinomas. The miR-181a-2* was only detected in salivary gland-derived adenoid cystic carcinomas. Conclusions: Through post-transcriptional regulation of the genes, the diverse expression of some miRNAs may partially explain the diverse clinical outcome of salivary gland-derived and breast-derived adenoid cystic carcinomas. Orv. Hetil., 2013, 154, 963-968. | Az adenoid cysticus carcinoma a nyálmirigyeket érintő rosszindulatú daganat, ritkán azonban az emlő mirigyeiből is kiindulhat. A nyálmirigyből kiinduló forma nagyon agresszív kimenetelt mutat, az emlőmirigy adenoid cysticus tumora azonban általában igen kedvező prognózissal bír. Célkitűzés: A szerzők célul tűzték ki az emlőmirigyből és nyálmirigyből kiinduló adenoid cysticus carcinoma esetek miRNS-mintázatának összehasonlítását. Módszer: Két-két, emlőből és nyálmirigyből származó adenoid cysticus carcinoma és egy-egy normális emlő- és nyálmirigyszövetet vizsgáltak. A miRNS-profi lt Affymetrix® Gene Chip segítségével határozták meg. Eredmények: Egyes miRNS-ek expressziója emlő- és nyálmirigy-eredetű tumorokban eltért a normális kontrolljukhoz képest: a let-7b expressziója a nyálmirigy-eredetű tumorokban fokozott, míg emlőmirigyből származó adenoid cysticus carcinoma szövetekben csökkent volt, a miR-24 expressziója pedig ezzel ellentétesen változott: emlőeredetű adenoid cysticus carcinoma szövetekben emelkedést mutatott, míg a nyálmirigy tumoraiban csökkent mértékben expresszálódott. A miR-181a-2* kizárólag a nyálmirigy-eredetű adenoid cysticus carcinoma esetekben volt detek tálható. Következtetések: A gének poszttranszkripcionális szabályozása révén egyes miRNS-ek eltérő expressziója részleges magyarázatot adhat a két szerv adenoid cysticus tumorainak eltérő klinikai lefolyására

Gender, hyperandrogenism and vitamin D deficiency related functional and morphological alterations of rat cerebral arteries

Hyperandrogenism is a risk factor of cerebrovascular diseases as androgens can alter markedly the regulation of cerebrovascular tone. We examined the combined impact of androgen excess and vitamin D deficiency (VDD), a common co-morbidity in hyperandrogenic disorders, on remodeling and testosterone-induced vascular responses of anterior cerebral arteries (ACA) in order to evaluate the interplay between androgens and VDD in the cerebral vasculature. Male and female Wistar rats were either fed with vitamin D deficient or vitamin D supplemented diet. Half of the female animals from both groups received transdermal testosterone treatment. After 8 weeks, vessel lumen, wall thickness and testosterone-induced vascular tone of isolated ACA were determined using pressure microangiometry and histological examination. Androgen receptor protein expression in the wall of cerebral arteries was examined using immunohistochemistry. In female rats only combined VDD and testosterone treatment decreased the lumen and increased the wall thickness of ACA. In males, however VDD by itself was able to decrease the lumen and increase the wall thickness. Vascular reactivity showed similar alterations: in females, testosterone constricted the ACA only after combined VDD and hyperandrogenism, whereas in males VDD resulted in increased testosterone-induced contractions in spite of decreased androgen receptor expression. In conclusion, a marked interplay between hyperandrogenism and VDD results in inward remodeling and enhanced testosterone-induced constrictions of cerebral arteries, which might compromise the cerebral circulation and thus, increase the risk of stroke in the long term. In addition, the early cerebrovascular manifestation of VDD appears to require androgen excess and thus, depends on gender

Vitamin D deficiency causes inward hypertrophic remodeling and alters vascular reactivity of rat cerebral arterioles

BACKGROUND AND PURPOSE: Vitamin D deficiency (VDD) is a global health problem, which can lead to several pathophysiological consequences including cardiovascular diseases. Its impact on the cerebrovascular system is not well understood. The goal of the present work was to examine the effects of VDD on the morphological, biomechanical and functional properties of cerebral arterioles. METHODS: Four-week-old male Wistar rats (n = 11 per group) were either fed with vitamin D deficient diet or received conventional rat chow with per os vitamin D supplementation. Cardiovascular parameters and hormone levels (testosterone, androstenedione, progesterone and 25-hydroxyvitamin D) were measured during the study. After 8 weeks of treatment anterior cerebral artery segments were prepared and their morphological, biomechanical and functional properties were examined using pressure microangiometry. Resorcin-fuchsin and smooth muscle actin staining were used to detect elastic fiber density and smooth muscle cell counts in the vessel wall, respectively. Sections were immunostained for eNOS and COX-2 as well. RESULTS: VDD markedly increased the wall thickness, the wall-to-lumen ratio and the wall cross-sectional area of arterioles as well as the number of smooth muscle cells in the tunica media. As a consequence, tangential wall stress was significantly lower in the VDD group. In addition, VDD increased the myogenic as well as the uridine 5'-triphosphate-induced tone and impaired bradykinin-induced relaxation. Decreased eNOS and increased COX-2 expression were also observed in the endothelium of VDD animals. CONCLUSIONS: VDD causes inward hypertrophic remodeling due to vascular smooth muscle cell proliferation and enhances the vessel tone probably because of increased vasoconstrictor prostanoid levels in young adult rats. In addition, the decreased eNOS expression results in endothelial dysfunction. These morphological and functional alterations can potentially compromise the cerebral circulation and lead to cerebrovascular disorders in VDD

Elastic components of the vessel wall.

<p>(A) Representative images of cerebral arterioles stained with Weigert’s resorcin-fuchsin. (B) Elastic fiber density did not differ between the groups according to measurement of green color intensity as a function of distance from the luminal surface measured on resorcin-fuchsin-stained segments.</p

The tangential wall stress of the cerebral arteries in relaxed condition.

<p>VDD caused a decrease in the tangential stress of the vessel wall throughout the entire pressure range under passive conditions (* p<0.05, n = 10–11).</p

Cerebral artery geometry and nucleus count of the smooth muscle layer.

<p>(A) VDD significantly increased the wall thickness (* p<0.05, n = 10–11) as well as (B) the wall thickness / lumen diameter ratio (** p<0.01, n = 10–11). (C) The cross-sectional area of the vessel walls increased significantly in VDD as compared to the Control group (* p<0.05, n = 9–9) at 50 mmHg intraluminal pressure. All these parameters were measured under passive conditions. (D) Significantly more nuclei were detected in the smooth muscle layer of anterior cerebral arteries of VDD animals as compared to controls (*** p<0.0001, n = 4–6). (E) The thickness of the tunica media was increased in the VDD group as compared to the control animals (* p<0.05, n = 4–4). (F) In addition, VDD significantly decreased the intima / media ratio of cerebral arteries (* p<0.05, n = 4–4).</p

Alterations of blood pressure in rodent models of VDD induced by VitD deficient feeding.

<p>Alterations of blood pressure in rodent models of VDD induced by VitD deficient feeding.</p

Physiological parameters and serum levels of hormones, 25-hydroxyvitamin D and glucose in the two experimental groups.

<p>Physiological parameters and serum levels of hormones, 25-hydroxyvitamin D and glucose in the two experimental groups.</p

Breast- and Salivary Gland-Derived Adenoid Cystic Carcinomas: Potential Post-Transcriptional Divergencies. A Pilot Study Based on miRNA Expression Profiling of Four Cases and Review of the Potential Relevance of the Findings

Adenoid cystic carcinoma (ACC) is a malignant tumor of the salivary glands but identical tumors can also arise from the breast. Despite their similar histomorphological appearance the salivary gland- and the breast-derived forms differ in their clinical features: while ACC of the salivary glands (sACC) have an agressive clinical course, the breast-derived form (bACC) shows a very favourable clinical outcome. To date no exact molecular alterations have yet been identified which would explain the diverse clinical features of the ACCs of different origin. In our pilot experiment we investigated the post-transcriptional features of ACC cases by performing microRNA-profiling on 2-2 bACC and sACC tissues and on 1-1 normal breast and salivary gland tissue. By comparing the microRNA-profiles of the investigated samples we identified microRNAs which were expressed differently in bACC and sACC cases according to their normal controls: 7 microRNAs were overexpressed in sACC cases and downexpressed in bACC tumors (let-7b, let-7c, miR-17, miR-20a, miR-24, miR-195, miR-768-3) while 9 microRNAs were downexpressed in sACC cases and overexpressed in bACC tissues (let-7e, miR-23b, miR-27b, miR-193b, miR-320a, miR-320c, miR-768-5p, miR-1280 and miR-1826) relative to their controls. We also identified 8 microRNAs which were only expressed in sACCs and one microRNA (miR-1234) which was only absent in sACC cases. By target predictor online databases potential targets of the these microRNAs were detected to identify genes that may play central role in the diverse cinical outcome of bACC and sACC cases

Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes

BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo