TY  - JOUR
AU  - Besenyi, Zsuzsanna
AU  - Ágoston, Gergely
AU  - Hemelein, Rita Adrienn
AU  - Bakos, Annamária
AU  - Nagy, Ferenc Tamás
AU  - Varga, Albert
AU  - Kovács, László
AU  - Pávics, László
TI  - Detection of myocardial inflammation by 18F-FDG-PET/CT in patients with systemic sclerosis without cardiac symptoms. a pilot study
TS  - a pilot study
JF  - CLINICAL AND EXPERIMENTAL RHEUMATOLOGY
J2  - CLIN EXP RHEUMATOL
VL  - 37 S119
PY  - 2019
IS  - 4
SP  - S88
EP  - S96
PG  - 9
SN  - 0392-856X
UR  - https://m2.mtmt.hu/api/publication/30399621
ID  - 30399621
AB  - Primary cardiac manifestation is a common complication of systemic sclerosis (SSc) with poor prognosis. The aim of the current study was to detect potential myocardial inflammation present in asymptomatic SSc patients by 18F-FDG-PET/CT and to investigate its relationship with early signs of myocardial dysfunction as detected by 2D speckle tracking echocardiography (2DSTE).Sixteen consecutive patients with SSc and 9 control patients without clinical evidence of cardiac involvement were enrolled in the study. On 18F-FDG-PET acquired images blood-pool normalised SUV ratio and heterogenity index (HI: standard deviation of SUV divided with mean SUV) were calculated. Within 24 hours all SSc patients underwent 2DSTE strain analysis.Eight of 16 SSc patients were found to be visually PET-positive and showed significantly higher myocardial 18F-FDG SUV ratio (1.78±0.74 vs. 0.98±0.03; p<0.05) and heterogenity index (0.13±0.02 vs. 0.05±0.02; p<0.001) as compared to the control group. FDG-PET/CT derived values did not differ significantly between visually PET-negative (8/16) and control patients (SUV ratio: 0.98±0.05 vs. 0.98±0.03; HI: 0.05±0.01 vs. 0.05±0.02). Global left ventricular longitudinal strain values did not differ significantly between PET-positive and negative patients (17.18±3.49% vs. 17.59±3.65%).Myocardial inflammation, as a potential sign of early cardiac involvement can be detected by 18-FDG-PET/CT in a considerable percentage of systemic sclerosis patients presenting without cardiac symptoms.
LA  - English
DB  - MTMT
ER  - 

TY  - JOUR
AU  - Gerlinger, Marco
AU  - Rowan, Andrew J
AU  - Horswell, Stuart
AU  - Math, M
AU  - Larkin, James
AU  - Endesfelder, David
AU  - Gronroos, Eva
AU  - Martinez, Pierre
AU  - Matthews, Nicholas
AU  - Stewart, Aengus
AU  - Tarpey, Patrick
AU  - Varela, Ignacio
AU  - Phillimore, Benjamin
AU  - Begum, Sharmin
AU  - McDonald, Neil Q
AU  - Butler, Adam
AU  - Jones, David
AU  - Raine, Keiran
AU  - Latimer, Calli
AU  - Santos, Claudio R
AU  - Nohadani, Mahrokh
AU  - Eklund, Aron C
AU  - Spencer-Dene, Bradley
AU  - Clark, Graham
AU  - Pickering, Lisa
AU  - Stamp, Gordon
AU  - Gore, Martin
AU  - Szállási, Zoltán
AU  - Downward, Julian
AU  - Futreal, P Andrew
AU  - Swanton, Charles
TI  - Intratumor heterogeneity and branched evolution revealed by multiregion sequencing.
JF  - NEW ENGLAND JOURNAL OF MEDICINE
J2  - NEW ENGL J MED
VL  - 366
PY  - 2012
IS  - 10
SP  - 883
EP  - 892
PG  - 10
SN  - 0028-4793
DO  - 10.1056/NEJMoa1113205
UR  - https://m2.mtmt.hu/api/publication/32695715
ID  - 32695715
N1  - Journal Article; Research Support, Non-U.S. Gov't
AB  - Intratumor heterogeneity may foster tumor evolution and adaptation and hinder personalized-medicine strategies that depend on results from single tumor-biopsy samples.To examine intratumor heterogeneity, we performed exome sequencing, chromosome aberration analysis, and ploidy profiling on multiple spatially separated samples obtained from primary renal carcinomas and associated metastatic sites. We characterized the consequences of intratumor heterogeneity using immunohistochemical analysis, mutation functional analysis, and profiling of messenger RNA expression.Phylogenetic reconstruction revealed branched evolutionary tumor growth, with 63 to 69% of all somatic mutations not detectable across every tumor region. Intratumor heterogeneity was observed for a mutation within an autoinhibitory domain of the mammalian target of rapamycin (mTOR) kinase, correlating with S6 and 4EBP phosphorylation in vivo and constitutive activation of mTOR kinase activity in vitro. Mutational intratumor heterogeneity was seen for multiple tumor-suppressor genes converging on loss of function; SETD2, PTEN, and KDM5C underwent multiple distinct and spatially separated inactivating mutations within a single tumor, suggesting convergent phenotypic evolution. Gene-expression signatures of good and poor prognosis were detected in different regions of the same tumor. Allelic composition and ploidy profiling analysis revealed extensive intratumor heterogeneity, with 26 of 30 tumor samples from four tumors harboring divergent allelic-imbalance profiles and with ploidy heterogeneity in two of four tumors.Intratumor heterogeneity can lead to underestimation of the tumor genomics landscape portrayed from single tumor-biopsy samples and may present major challenges to personalized-medicine and biomarker development. Intratumor heterogeneity, associated with heterogeneous protein function, may foster tumor adaptation and therapeutic failure through Darwinian selection. (Funded by the Medical Research Council and others.).
LA  - English
DB  - MTMT
ER  -