Publications of Aurélie LADANG
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See detailParathormone, bone alkaline phosphatase and 25-hydroxyvitamin D status in a large cohort of 1200 children and teenagers.
LADANG, Aurélie ULiege; ROUSSELLE, Olivier ULiege; Huyghebaert, Loreen ULiege et al

in Acta Clinica Belgica (2020)

OBJECTIVES: 25-Hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone alkaline phosphatase (BALP) are biomarkers of calcium/phosphate metabolism and bone turnover. Although vitamin D deficiency is ... [more ▼]

OBJECTIVES: 25-Hydroxyvitamin D (25(OH)D), parathyroid hormone (PTH) and bone alkaline phosphatase (BALP) are biomarkers of calcium/phosphate metabolism and bone turnover. Although vitamin D deficiency is a well-known cause of secondary hyperparathyroidism, few studies have considered vitamin D status when establishing reference ranges. In this study, we report PTH levels according to the vitamin D status and BALP levels in a large cohort of 1200 children. Additionally, we provide PTH pediatric reference values according to 25(OH)D status as well as BALP pediatric reference ranges. METHODS: Serum samples from 1200 children (equally distributed from 5 months to 20 years old) who underwent blood sampling for allergy exploration were used to quantify 25(OH)D, PTH and BALP. RESULTS: The percentage of vitamin D deficient children (<20 ng/ml) progressively increased during childhood starting from 7% in the 0 to 2 year-old subgroup to a mean of at least 50% among teenagers. PTH levels inversely mirrored 25(OH)D concentrations for all age and gender subgroups, and 25(OH)D deficient subgroups presented higher PTH levels than their non-deficient counterparts. In the non-deficient 25(OH)D population, PTH levels were the highest at 11 years old for girls and 14 years old for boys. BALP results were slightly increased during childhood and showed a constant decrease during teenage years starting from 12 years old for girls and 14 years old for boys. CONCLUSION: Our results highlight the inverse relationship between PTH and 25(OH)D in children and the need for a well characterized 25(OH)D population to establish pediatric reference ranges for PTH. [less ▲]

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See detailEvaluation of a panel of microRNAs that predicts fragility fracture risk: a pilot study
LADANG, Aurélie ULiege; Beaudart, Charlotte ULiege; Locquet, Médéa ULiege et al

in Calcified Tissue International (2020), 106

The assessment of fragility fracture risk based on bone densitometry and FRAX°, although commonly used, has shown some limitations. MicroRNAs (miRNAs) are promising biomarkers known to regulate post ... [more ▼]

The assessment of fragility fracture risk based on bone densitometry and FRAX°, although commonly used, has shown some limitations. MicroRNAs (miRNAs) are promising biomarkers known to regulate post-transcriptional gene expression. Many studies have already shown that microRNAs are involved in bone homeostasis by modulating osteoblast and osteoclast gene expression. In this pilot study, we investigated the ability of an miRNA panel (namely, the OsteomiR° score) to predict fragility fracture risk in older people. miRNAs were extracted from the sera of 17 persons who developed a fracture within 3 years of collecting the serum and 16 persons who did not experience fractures in the same period. Nineteen miRNAs known to be involved in bone homeostasis were assessed, and 10 miRNAs were employed to calculate the OsteomiR° score. We found a trend towards higher OsteomiR° scores in individuals who experienced fractures compared to control subjects. The most suitable cut-off that maximized sensitivity and specificity was determined by ROC curve analysis, and a positive predictive value of 68% and a sensitivity of 76% were obtained. The OsteomiR° score was higher in osteopenic and osteoporotic subjects compared to subjects with a normal T score. Additionally, the OsteomiR° score predicted more fracture events than the recommended “need-to-treat” thresholds based on FRAX° 10-year probability. miRNAs reflect impairments in bone homeostasis several years before the occurrence of a fracture. The OsteomiR° score seems to be a promising miRNA panel for fragility fracture risk prediction and might have added value compared to FRAX°. Given the limited cohort size, further studies should be dedicated to validating the OsteomiR° score. [less ▲]

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See detailSimultaneous measurement of 25(OH)-vitamin D and 24,25(OH)2-vitamin D to define cut-offs for CYP24A1 mutation and vitamin D deficiency in a population of 1200 young subjects.
Cavalier, Etienne ULiege; Huyghebaert, Loreen ULiege; ROUSSELLE, Olivier ULiege et al

in Clinical chemistry and laboratory medicine (2020), 58(2), 197-201

Background Simultaneous measurement of 25(OH)D and 24,25(OH)2D is a new tool for predicting vitamin D deficiency and allows evaluating CYP24A1 lack of function. Interpretation of 24,25(OH)2D should be ... [more ▼]

Background Simultaneous measurement of 25(OH)D and 24,25(OH)2D is a new tool for predicting vitamin D deficiency and allows evaluating CYP24A1 lack of function. Interpretation of 24,25(OH)2D should be performed according to 25(OH)D levels and a ratio, called the vitamin D metabolite ratio (VMR) has been proposed for such a purpose. Unfortunately, the VMR can be expressed in different ways and cannot be used if 24,25(OH)2D concentrations are undetectable. Here, we propose evaluating the enzyme activity taking into consideration the probability that a normal population presents undetectable 24,25(OH)2D concentrations according to 25(OH)D levels. We thus retrospectively measured 25(OH)D and 24,25(OH)2D in a population of 1200 young subjects to evaluate the 25(OH)D threshold above which the enzyme was induced. Methods Serum samples from 1200 infants, children, adolescent and young adults were used to simultaneously quantify 25(OH)D and 24,25(OH)2D by LCMS/MS. Results Median (interquartile range [IQR]) levels were 20.6 (14.4-27.2) ng/mL for 25(OH)D. 172 subjects (14.3%) presented 24,25(OH)2D values below the LOQ. When 25(OH)D values were <11 ng/mL, 63.1% of subjects presented undetectable 24,25(OH)2D concentrations. Percentage decreased with increasing 25(OH)D values to become 19.7% for 25(OH)D comprised between 12 and 15 ng/mL, 5.1% for 25(OH)D between 16 and 20 and 0.7% for 25(OH)D >21 ng/mL. Conclusions We suggest using a statistical approach to evaluate CYP24A1 function according to 25(OH)D concentrations. Our results also show that vitamin D deficiency, as defined biochemically, could be around 20 ng/mL in infants, children, adolescent and young adults and that vitamin D deficiency could be evaluated on a more individual basis. [less ▲]

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See detailFragility fracture risk prediction in elderly people based on a micro RNA panel.
LADANG, Aurélie ULiege; Beaudart, Charlotte ULiege; Locquet, Médéa ULiege et al

in Osteoporosis International (2019, July), 30(S2), 299-300

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See detailUnconventional richter syndrome with plasmablastic transformation
LADANG, Aurélie ULiege; SIMUL, Mickael ULiege; SOMJA, Joan ULiege et al

Poster (2017, February)

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See detailRichter syndrome with plasmablastic lymphoma
LADANG, Aurélie ULiege; SIMUL, Mickael ULiege; SOMJA, Joan ULiege et al

Conference (2017, February)

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See detailEtude rétrospective du bilan thyroïdien: définition de valeurs de référence pédiatriques
LADANG, Aurélie ULiege; VRANKEN, Laura ULiege; LUYCKX, Françoise ULiege et al

in Revue Médicale de Liège (2017)

Defining reference range is an essential tool for diagnostic. Age and sexe influences on thyroid hormone levels have been already discussed. In this study, we are defining a new pediatric reference range ... [more ▼]

Defining reference range is an essential tool for diagnostic. Age and sexe influences on thyroid hormone levels have been already discussed. In this study, we are defining a new pediatric reference range for TSH, FT3 and FT4 for Cobas C6000 analyzer. To do so, we have taken in account 0 to 18 year old outclinic patients. During the first year of life, thyroid hormone levels change dramatically before getting stabilized around 3 years old. We also compared our results to those obtained in a Canadian large-scale prospective study (the CALIPER initiative). [less ▲]

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See detailUnexpected high levels of Cobalamin (Vitamin B12): Numerous interferences are decreased by PEG treatment.
LADANG, Aurélie ULiege; VRANKEN, Laura ULiege; CAVALIER, Etienne ULiege

Poster (2016, October)

Cobalamin (Vitamin B12) deficiency is a common cause of anemia. High levels of serum cobalamin is mainly due to cobalamin supplementation. It has also been associated with hematological malignancies ... [more ▼]

Cobalamin (Vitamin B12) deficiency is a common cause of anemia. High levels of serum cobalamin is mainly due to cobalamin supplementation. It has also been associated with hematological malignancies, liver or renal diseases. Cobalamin is sometimes found elevated in autoimmune disorders and infectious diseases but concerns are raised on the fact that those serum increases might be due to interference with immunoassays. Those data’s shed the lights on the high prevalence of interference in patients with unexpected high cobalamin level. Precipitation with PEG appears to be an easy and costless method to increase the reliability of cobalamin dosage. In accordance with our results, we recommand to treat systematically every serum with a cobalamin >1500 ng/L. [less ▲]

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See detailtRNA modification: Elogator promotes metastasis in breast cancer
Delaunay, Sylvain ULiege; Rapino, Francesca ULiege; Zhou, Zhaoli ULiege et al

Conference (2016, January 25)

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the ... [more ▼]

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the wobble U34 base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, are upregulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer. Mechanistically, ELP3 and CTU1/2 support cellular invasion through the translation of the oncoprotein DEK. As a result, DEK promotes the IRES-dependent translation of the pro-invasive transcription factor LEF1. Consistently, a DEK mutant, whose codon composition is independent of U34 mcm5s2-tRNA modification, escapes the ELP3- and CTU1- dependent regulation and restores the IRES-dependent LEF1 expression. Our results demonstrate the key role of U34 tRNA modification to support specific translation during breast cancer progression and highlight a functional link between tRNA modification- and IRES-dependent translation during tumor cell invasion and metastasis. [less ▲]

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See detailElp3 drives Wnt-dependent tumor initiation and regeneration in the intestine
LADANG, Aurélie ULiege; Rapino, Francesca ULiege; Heukamp, Lukas et al

in Journal of Experimental Medicine (2015), 212(12), 2057-75

Tumor initiation in the intestine can rapidly occur from Lgr5(+) crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer ... [more ▼]

Tumor initiation in the intestine can rapidly occur from Lgr5(+) crypt columnar stem cells. Dclk1 is a marker of differentiated Tuft cells and, when coexpressed with Lgr5, also marks intestinal cancer stem cells. Here, we show that Elp3, the catalytic subunit of the Elongator complex, is required for Wnt-driven intestinal tumor initiation and radiation-induced regeneration by maintaining a subpool of Lgr5(+)/Dclk1(+)/Sox9(+) cells. Elp3 deficiency dramatically delayed tumor appearance in Apc-mutated intestinal epithelia and greatly prolonged mice survival without affecting the normal epithelium. Specific ablation of Elp3 in Lgr5(+) cells resulted in marked reduction of polyp formation upon Apc inactivation, in part due to a decreased number of Lgr5(+)/Dclk1(+)/Sox9(+) cells. Mechanistically, Elp3 is induced by Wnt signaling and promotes Sox9 translation, which is needed to maintain the subpool of Lgr5(+)/Dclk1(+) cancer stem cells. Consequently, Elp3 or Sox9 depletion led to similar defects in Dclk1(+) cancer stem cells in ex vivo organoids. Finally, Elp3 deficiency strongly impaired radiation-induced intestinal regeneration, in part because of decreased Sox9 protein levels. Together, our data demonstrate the crucial role of Elp3 in maintaining a subpopulation of Lgr5-derived and Sox9-expressing cells needed to trigger Wnt-driven tumor initiation in the intestine. [less ▲]

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See detailElongator: mcm5s2 modification fosters breast cancer metastasis
Delaunay, Sylvain ULiege; Rapino, Francesca ULiege; Zhou, Zhaoli ULiege et al

Scientific conference (2015, March 09)

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the ... [more ▼]

Quantitative and qualitative changes in mRNA translation occur in tumor cells and support cancer progression and metastasis. Post-transcriptional nucleoside modifications of transfer RNAs (tRNAs) at the wobble U34 base are highly conserved and contribute to translation fidelity. Here, we show that ELP3 and CTU1/2, partner enzymes in U34 mcm5s2-tRNA modification, are upregulated in human breast cancers and sustain metastasis. Elp3 genetic ablation strongly impaired invasion and metastasis formation in the PyMT model of invasive breast cancer. Mechanistically, ELP3 and CTU1/2 support cellular invasion through the translation of the oncoprotein DEK. As a result, DEK promotes the IRES-dependent translation of the pro-invasive transcription factor LEF1. Consistently, a DEK mutant, whose codon composition is independent of U34 mcm5s2-tRNA modification, escapes the ELP3- and CTU1- dependent regulation and restores the IRES-dependent LEF1 expression. Our results demonstrate the key role of U34 tRNA modification to support specific translation during breast cancer progression and highlight a functional link between tRNA modification- and IRES-dependent translation during tumor cell invasion and metastasis. [less ▲]

Detailed reference viewed: 103 (13 ULiège)
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See detailElongator promotes breast cancer metastasis
Delaunay, Sylvain ULiege; Rapino, Francesca ULiege; Heukamp, Lukas et al

Poster (2015, March)

Elongator is a protein complex (Elp1-6) involved in diverse cellular processes, such as protein acetylation and tRNA modification and whose function is essential for cell migration and neuronal ... [more ▼]

Elongator is a protein complex (Elp1-6) involved in diverse cellular processes, such as protein acetylation and tRNA modification and whose function is essential for cell migration and neuronal differentiation. Although it is well established that tumor development involves modifications of acetylation-deacetylation dynamics, as well as changes in protein translation, the role of Elongator in tumor initiation and invasion remains to be investigated in vivo. We generated a mouse model in which the Elp3 gene, encoding the catalytic subunit of the complex, is conditionally inactivated in the mammary gland epithelium by using the MMTV-CRE transgenic mouse. The role of Elp3 in tumor development and metastasis formation is then assessed in the PyMT model of invasive breast cancer. [less ▲]

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See detailElongator drives breast cancer initiation and metastasis formation
Delaunay, Sylvain ULiege; Heukamp, Lukas; Zhou, Zhaoli ULiege et al

Poster (2014, May 08)

Elongator complex functions in diverse cellular processes, such as protein acetylation and tRNA modification, and is essential for cell migration and neuronal differentiation. Although it is well ... [more ▼]

Elongator complex functions in diverse cellular processes, such as protein acetylation and tRNA modification, and is essential for cell migration and neuronal differentiation. Although it is well established that tumor development involves modifications of acetylation-deacetylation dynamics as well as changes in protein translation, the role of Elongator in tumor initiation and invasion remains to be studied. Breast cancer is amongst the most common cause of cancer-related deaths in women, and the majority of them involved metastasis dissemination. In vitro, the inactivation of elongator affects the migration and the clonogenic potential of breast cancer cells. In vivo, expression of the ELP1 and Elp3 subunits is elevated over tumor development and in lung metastasis of PyMT-MMTV breast cancer mice. To address the role of elongator in tumor development in vivo, we generated a mouse model in which the catalytic subunit Elp3 is specifically invalidated in the mammary epithelium (Elp3ΔMEC), that we crossed with the PyMT-MMTV model of breast cancer. Elp3 ablation in the mammary epithelium of the PyMT mice caused a delay in primary tumor initiation and reduced metastasis to distal sites. Moreover, PyMT tumor cells formed less mammospheres in the absence of Elp3. Together, our data demonstrate that elongator complex is a key actor in breast cancer initiation and dissemination. [less ▲]

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