302. FIBROID ASSOCIATED HEAVY MENSTRUAL BLEEDING: CORRELATION OF CLINICAL SYMPTOMS, DOPPLER ULTRASOUND ASSESSMENT OF VASCULATURE AND TISSUE GENE EXPRESSION PROFILES

2010 ◽  
Vol 22 (9) ◽  
pp. 102
Author(s):  
S. Tsiligiannis ◽  
M. Zaitseva ◽  
P. Coombs ◽  
P. Shekleton ◽  
B. Vollenhoven ◽  
...  

Understanding of the mechanisms that cause fibroid associated heavy menstrual bleeding (HMB) is limited. Despite many fibroids having a highly vascular peri-fibroid myometrial (PFM) zone, angiogenic gene expression in this area has never been investigated. The aim of this study was to correlate clinical symptoms, ultrasound appearances and tissue gene expression profiles in women scheduled for hysterectomy due to symptomatic fibroids. We hypothesised that fibroid heterogeneity, colour flow and spectral Doppler resistive indices would correlate with differences in gene expression profiles. It was thought and that increased peri-fibroid gene expression of key angiogenic genes would correlate with increased peri-fibroid vascularity. N = 6 patients underwent B-mode, colour and spectral Doppler ultrasound assessment. Following hysterectomy tissue samples collected from three areas – fibroid, PFM and distant myometrium (DM) were analysed using quantitative RT-PCR and a customised angiogenesis PCR array. A higher mean peak systolic velocity (PSV) in the PFM region when compared to mean PSV within the fibroid (P < 0.001) was seen. Differences in angiogenic gene expression were consistent with the heterogeneity of the clinical data collected. One fibroid sample showed dissimilar gene expression to all other fibroids; at ultrasound and sample collection significant degenerative features were observed. Fibroid heterogeneity within a single uterus was also demonstrated, with two fibroids from the one uterus having significantly dissimilar gene profiles and ultrasound appearances. No differences in gene expression were found between PFM and DM. Despite this, gene interaction maps showed different interaction of genes between fibroid and PFM regions compared to genes between the fibroid and the DM. These are the first molecular data demonstrating that the PFM region may be functionally distinct from distant myometrium.

2009 ◽  
Vol 161 (1) ◽  
pp. 141-152 ◽  
Author(s):  
Cecilia Laurell ◽  
David Velázquez-Fernández ◽  
Kristina Lindsten ◽  
Christofer Juhlin ◽  
Ulla Enberg ◽  
...  

ObjectiveTumours in the adrenocortex are common human tumours. Malignancy is however, rare, the yearly incidence being 0.5–2 per million inhabitants, but associated with a very aggressive behaviour. Adrenocortical tumours are often associated with altered hormone production with a variety of clinical symptoms. The aggressiveness of carcinomas together with the high frequency of adenomas calls for a deeper understanding of the underlying biological mechanisms and an improvement of the diagnostic possibilities.MethodsMicroarray gene expression analysis was performed in tumours of adrenocortex with emphasis on malignancy as well as hormonal activity. The sample set consisted of 17 adenomas, 11 carcinomas and 4 histological normal adrenocortexes. RNA from these was hybridised according to a reference design on microarrays harbouring 29 760 human cDNA clones. Confirmation was performed with quantitative real time-PCR and western blot analysis.ResultsUnsupervised clustering to reveal relationships between samples based on the entire gene expression profile resulted in two subclusters; carcinomas and non-cancer specimens. A large number of genes were accordingly found to be differentially expressed comparing carcinomas to adenomas. Among these were IGF2, FGFR1 and FGFR4 in growth factor signalling the most predominant and also the USP4, UBE2C and UFD1L in the ubiquitin-proteasome pathway. Moreover, two subgroups of carcinomas were identified with different survival outcome, suggesting that survival prediction can be made on the basis of gene expression profiles. Regarding adenomas with aldosterone overproduction, OSBP and VEGFB were among the most up-regulated genes compared with the other samples.ConclusionsAdrenocortical carcinomas are associated with a distinct molecular signature apparent in their gene expression profiles. Differentially expressed genes were identified associated with malignancy, survival as well as hormonal activity providing a resource of candidate genes for an exploration of possible drug targets and diagnostic and prognostic markers.


2008 ◽  
Vol 89 (1) ◽  
pp. 51-57 ◽  
Author(s):  
David M Mutch ◽  
Joan Tordjman ◽  
Véronique Pelloux ◽  
Blaise Hanczar ◽  
Corneliu Henegar ◽  
...  

2006 ◽  
Vol 31 (5) ◽  
pp. 565-573 ◽  
Author(s):  
Hongbao Wang ◽  
Hui Li ◽  
Qigui Wang ◽  
Yuxiang Wang ◽  
Huabin Han ◽  
...  

Life Sciences ◽  
2008 ◽  
Vol 83 (1-2) ◽  
pp. 35-42 ◽  
Author(s):  
Wei Zhang ◽  
Mary Anne Della-Fera ◽  
Diane L. Hartzell ◽  
Dorothy Hausman ◽  
Clifton A. Baile

2021 ◽  
Vol 22 (23) ◽  
pp. 12876
Author(s):  
Scott W. Walsh ◽  
Marwah Al Dulaimi ◽  
Kellie J. Archer ◽  
Jerome F. Strauss

Neutrophils are activated and extensively infiltrate blood vessels in preeclamptic women. To identify genes that contribute to neutrophil activation and infiltration, we analyzed the transcriptomes of circulating neutrophils from normal pregnant and preeclamptic women. Neutrophils were collected at 30 weeks’ gestation and RNA and DNA were isolated for RNA sequencing and 5-hydroxy-methylcytosine (5-hmC) sequencing as an index of dynamic changes in neutrophil DNA methylation. Women with normal pregnancy who went on to develop mild preeclampsia at term had the most uniquely expressed genes (697) with 325 gene ontology pathways upregulated, many related to neutrophil activation and function. Women with severe preeclampsia who delivered prematurely had few pathways up- or downregulated. Cluster analysis revealed that gene expression in women with severe preeclampsia was an inverse mirror image of gene expression in normal pregnancy, while gene expression in women who developed mild preeclampsia was remarkably different from both. DNA methylation marks, key regulators of gene expression, are removed by the action of ten-eleven translocation (TET) enzymes, which oxidize 5-methylcytosines (5mCs), resulting in locus-specific reversal of DNA methylation. DNA sequencing for 5-hmC revealed no differences among the three groups. Genome-wide DNA methylation revealed extremely low levels in circulating neutrophils suggesting they are de-methylated. Collectively, these data demonstrate that neutrophil gene expression profiles can distinguish different preeclampsia phenotypes, and in the case of mild preeclampsia, alterations in gene expression occur well before clinical symptoms emerge. These findings serve as a foundation for further evaluation of neutrophil transcriptomes as biomarkers of preeclampsia phenotypes. Changes in DNA methylation in circulating neutrophils do not appear to mediate differential patterns of gene expression in either mild or severe preeclampsia.


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