14 research outputs found
A D-vitamin metabolizmusa humán hepatocellularis carcinomában és az azt körülvevő tumormentes májszövetben
Absztrakt
Bevezetés: Az 1,25-dihidroxi-D3-vitamin tumorellenes
hatása hepatocellularis carcinomában már részben ismert.
Célkitűzés: Az 1,25-dihidroxi-D3-vitamint
inaktiváló CYP24A1-mRNS- és fehérjeexpresszió, az aktiváló
CYP27B1- és a VDR-mRNS-expresszió mértékének
összehasonlítása humán hepatocellularis carcinomában és az azt körülvevő
tumormentes májszövetben. Módszer: 13 beteg friss fagyasztott
májszövetmintáját a CYP24A1-mRNS- és fehérje-, 36 beteg
paraffinba ágyazott májszövetmintáját használtuk a VDR- és a
CYP27B1-mRNS-expresszió kimutatására. Az mRNS-expressziót
RT-PCR-rel, a fehérjét immunhisztokémiai vizsgálatokkal mértük.
Eredmények: A hepatocellularis carcinomaminták többségében
kimutatható volt a CYP24A1-mRNS-expresszió, míg a nem tumoros
májszövetminták egyikében sem. A CYP27B1- és VDR-expresszió
szignifikánsan alacsonyabb hepatocellularis carcinomában a tumormentes
májszövethez képest (p<0,05). A CYP24A1-mRNS-expressziót
fehérjeszintézis követi. Következtetések: A
CYP24A1 inaktiváló enzim jelenléte, az aktiváló
CYP27B1 és a VDR csökkent expressziója humán
hepatocellularis carcinomában a D-vitamin csökkent helyi aktivitására enged
következtetni, mint egy menekülő mechanizmus a tumor részéről a D-vitamin
antitumorhatása ellen. Orv. Hetil., 2016, 157(48),
1910–1918.
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Abstract
Introduction: 1,25-Dihydroxy vitamin D3 mediates
antitumor effects in hepatocellular carcinoma. Aim: We examined
mRNA and protein expression differences in 1,25-Dihydroxy vitamin
D3-inactivating CYP24A1, mRNA of activating
CYP27B1 enzymes, and that of VDR between human
hepatocellular carcinoma and surrounding non-tumorous liver.
Methods: Snap-frozen tissues from 13 patients were studied
for mRNA and protein expression of CYP24A1. Paraffin-embedded
tissues from 36 patients were used to study mRNA of VDR and
CYP27B1. mRNA expression was measured by RT-PCR,
CYP24A1 protein was detected by immunohistochemistry.
Results: Expression of VDR and CYP27B1 was
significantly lower in hepatocellular carcinoma compared with non-tumorous liver
(p<0.05). The majority of the HCC samples expressed CYP24A1
mRNA, but neither of the non-tumorous liver. The gene activation was followed by
CYP24A1 protein synthesis. Conclusions:
The presence of CYP24A1 mRNA and the reduced expression of VDR
and CYP27B1 mRNA in human hepatocellular carcinoma samples
indicate decreased bioavailability of 1,25-Dihydroxy vitamin D3,
providing an escape mechanism from the anti-tumor effect. Orv. Hetil., 2016,
157(48), 1910–1918
High tricellulin expression is associated with better survival in human hepatoblastoma.
AIMS
The more differentiated fetal component of hepatoblastoma (HB) is characterized by increased expression of tight junction (TJ) proteins claudin-1 and -2 when compared with embryonal component. Expression patterns of the recently identified TJ protein tricellulin and the epigenetic regulator enzyme EZH2 were investigated in epithelial subtypes of HB and related to survival.
METHODS AND RESULTS
Twenty-one cases of epithelial HBs subtyped as pure fetal (n = 12) and embryonal/fetal (n = 9), along with 16 non-tumorous samples from surrounding liver, were analysed by immunohistochemistry for tricellulin, β-catenin and EZH2 expression. No significant differences were revealed in overall survival between fetal and embryonal/fetal types of HBs. The fetal component, however, showed considerably increased tricellulin expression while the embryonal component displayed significantly increased nuclear EZH2 positivity, in comparison to other epithelial subtypes and non-tumorous surrounding hepatocytes. Strong nuclear β-catenin staining was notably more frequent in embryonal than in fetal types. High tricellulin expression was associated with significantly increased overall survival (P = 0.03), while elevated EZH2 expression was linked to the presence of distant metastases (P = 0.013).
CONCLUSIONS
Our data indicate that patients with treated HBs showing high expression of tricellulin have significantly better overall survival, independent of histological subtype. Increased nuclear expression of EZH2 was associated with the presence of distant metastases
Sa1500 – Alcohol Induced Il-17A Production in Paneth Cells Amplifies Endoplasmic Reticulum Stress and Inflammasome-Il-18 Activation in the Proximal Small Intestine in Mice
Design and rationale for the Myocardial Stem Cell Administration After Acute Myocardial Infarction (MYSTAR) Study: A multicenter, prospective, randomized, single-blind trial comparing early and late intracoronary or combined (percutaneous intramyocardial and intracoronary) administration of nonselected autologous bone marrow cells to patients after acute myocardial infarction
BACKGROUND:
Previous data suggest that bone marrow-derived stem cells (BM-SCs) decrease the infarct size and beneficially affect the postinfarction remodeling.
METHODS:
The Myocardial Stem Cell Administration After Acute Myocardial Infarction Study is a multicenter, prospective, randomized, single-blind clinical trial designed to compare the early and late intracoronary or combined (percutaneous intramyocardial and intracoronary) administration of BM-SCs to patients after acute myocardial infarction (AMI) with reopened infarct-related artery. The primary end points are the changes in resting myocardial perfusion defect size and left ventricular ejection fraction (gated single photon emission computed tomography [SPECT] scintigraphy) 3 months after BM-SCs therapy. The secondary end points relate to evaluation of (1) the safety and feasibility of the application modes, (2) the changes in left ventricular wall motion score index (transthoracic echocardiography), (3) myocardial voltage and segmental wall motion (NOGA mapping), (4) left ventricular end-diastolic and end-systolic volumes (contrast ventriculography), and (5) the clinical symptoms (Canadian Cardiovascular Society [CCS] anina score and New York Heart Association [NYHA] functional class) at follow-up. Three hundred sixty patients are randomly assigned into 1 of 4 groups: group A, early treatment (21-42 days after AMI) with intracoronary injection; group B, early treatment with combined application; group C, late treatment (3 months after AMI) with intracoronary delivery; and group D, late treatment with combined administration of BM-SCs. Besides the BM-SCs therapy, the standardized treatment of AMI is applied in all patients.
CONCLUSIONS:
The Myocardial Stem Cell Administration After Acute Myocardial Infarction Trial is the first randomized trial to investigate the effects of the combined (intramyocardial and intracoronary) and the intracoronary mode of delivery of BM-SCs therapy in the early and late periods after AMI
Design and rationale for the Myocardial Stem Cell Administration After Acute Myocardial Infarction (MYSTAR) Study: a multicenter, prospective, randomized, single-blind trial comparing early and late intracoronary or combined (percutaneous intramyocardial and intracoronary) administration of nonselected autologous bone marrow cells to patients after acute myocardial infarction
Combined delivery approach of bone marrow mononuclear stem cells early and late after myocardial infarction: the MYSTAR prospective, randomized study
Increased Expression of Claudin-1 and Claudin-7 in Liver Cirrhosis and Hepatocellular Carcinoma.
Claudins have been reported to be differentially regulated in malignancies and implicated in the process of carcinogenesis and tumor progression. Claudin-1 has been described as key factor in the entry of hepatitis C virus (HCV) into hepatocytes and as promoter of epithelial-mesenchymal transition in liver cells. The objective of the current study was to characterize claudin expression in hepatocellular carcinoma (HCC) as well as HCC-surrounding and normal liver samples with respect to cirrhosis and HCV infection. Expression of claudin-1, -2, -3, -4, and -7 was measured by morphometric analysis of immunohistochemistry, and Western blotting in 30 HCCs with 30 corresponding non-tumorous tissues and 6 normal livers. Claudin-1 and -7 protein expression was found significantly elevated in cirrhosis when compared with non-cirrhotic liver. HCCs developed in cirrhotic livers showed even higher expression of claudin-1 contrary to decreased claudin-7 expression when compared with cirrhosis. With reference to HCV status, HCCs or surrounding livers of HCV-infected samples did not show significant alterations in claudin expression when compared with HCV-negative specimens. Cirrhotic transformation associates with elevated claudin-1 and -7 expressions in both non-tumorous liver and HCC. The fact that no significant differences in claudin expression were found regarding HCV-positivity in our sample set suggests that HCV infection alone does not induce a major increase in the total amount of its entry co-factor claudin-1. Increased expression of claudin-1 seems to be a consequence of cirrhotic transformation and might contribute to a more effective HCV entry and malignant transformation