TY  - JOUR
A1  - Liu, Dan
A1  - Hu, Kai
A1  - Niemann, Markus
A1  - Herrmann, Sebastian
A1  - Cikes, Maja
A1  - Störk, Stefan
A1  - Beer, Meinrad
A1  - Gaudron, Philipp Daniel
A1  - Morbach, Caroline
A1  - Knop, Stefan
A1  - Geissinger, Eva
A1  - Ertl, Georg
A1  - Bijnens, Bart
A1  - Weidemann, Frank
T1  - Impact of Regional Left Ventricular Function on Outcome for Patients with AL Amyloidosis
JF  - PLoS ONE
N2  - Objectives
The aim of this study was to explore the left ventricular (LV) deformation changes and the potential impact of deformation on outcome in patients with proven light-chain (AL) amyloidosis and LV hypertrophy.

Background
Cardiac involvement in AL amyloidosis patients is associated with poor outcome. Detecting regional cardiac function by advanced non-invasive techniques might be favorable for predicting outcome.

Methods
LV longitudinal, circumferential and radial peak systolic strains (Ssys) were assessed by speckle tracking imaging (STI) in 44 biopsy-proven systemic AL amyloidosis patients with LV hypertrophy (CA) and in 30 normal controls. Patients were divided into compensated (n = 18) and decompensated (n = 26) group based on clinical assessment and followed-up for a median period of 345 days.

Results
Ejection fraction (EF) was preserved while longitudinal Ssys (LSsys) was significantly reduced in both compensated and decompensated groups. Survival was significantly reduced in decompensated group (35% vs. compensated 78%, P = 0.001). LSsys were similar in apical segments and significantly reduced in basal segments between two patient groups. LSsys at mid-segments were significantly reduced in all LV walls of decompensated group. Patients were further divided into 4 subgroups according to the presence or absence of reduced LSsys in no (normal), only basal (mild), basal and mid (intermediate) and all segments of the septum (severe). This staging revealed continuously worse prognosis in proportion to increasing number of segments with reduced LSsys (mortality: normal 14%, mild 27%, intermediate 67%, and severe 64%). Mid-septum LSsys<11% suggested a 4.8-fold mortality risk than mid-septum LSsys≥11%. Multivariate regression analysis showed NYHA class and mid-septum LSsys were independent predictors for survival.

Conclusions
Reduced deformation at mid-septum is associated with worse prognosis in systemic amyloidosis patients with LV hypertrophy.
KW  - regression analysis
KW  - ejection fraction
KW  - echocardiography
KW  - cardiac transplantation
KW  - deformation
KW  - amyloidosis
KW  - prognosis
KW  - stem cell transplantation
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-130293
VL  - 8
IS  - 3
ER  - 
TY  - JOUR
A1  - Jessen, Christina
A1  - Kreß, Julia K. C.
A1  - Baluapuri, Apoorva
A1  - Hufnagel, Anita
A1  - Schmitz, Werner
A1  - Kneitz, Susanne
A1  - Roth, Sabine
A1  - Marquardt, André
A1  - Appenzeller, Silke
A1  - Ade, Casten P.
A1  - Glutsch, Valerie
A1  - Wobser, Marion
A1  - Friedmann-Angeli, José Pedro
A1  - Mosteo, Laura
A1  - Goding, Colin R.
A1  - Schilling, Bastian
A1  - Geissinger, Eva
A1  - Wolf, Elmar
A1  - Meierjohann, Svenja
T1  - The transcription factor NRF2 enhances melanoma malignancy by blocking differentiation and inducing COX2 expression
JF  - Oncogene
N2  - The transcription factor NRF2 is the major mediator of oxidative stress responses and is closely connected to therapy resistance in tumors harboring activating mutations in the NRF2 pathway. In melanoma, such mutations are rare, and it is unclear to what extent melanomas rely on NRF2. Here we show that NRF2 suppresses the activity of the melanocyte lineage marker MITF in melanoma, thereby reducing the expression of pigmentation markers. Intriguingly, we furthermore identified NRF2 as key regulator of immune-modulating genes, linking oxidative stress with the induction of cyclooxygenase 2 (COX2) in an ATF4-dependent manner. COX2 is critical for the secretion of prostaglandin E2 and was strongly induced by H\(_2\)O\(_2\) or TNFα only in presence of NRF2. Induction of MITF and depletion of COX2 and PGE2 were also observed in NRF2-deleted melanoma cells in vivo. Furthermore, genes corresponding to the innate immune response such as RSAD2 and IFIH1 were strongly elevated in absence of NRF2 and coincided with immune evasion parameters in human melanoma datasets. Even in vitro, NRF2 activation or prostaglandin E2 supplementation blunted the induction of the innate immune response in melanoma cells. Transcriptome analyses from lung adenocarcinomas indicate that the observed link between NRF2 and the innate immune response is not restricted to melanoma.
KW  - NRF2
KW  - melanoma malignancy
KW  - COX2 expression
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-235064
SN  - 0950-9232
VL  - 39
ER  -