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8 results on '"Conemans, E B"'

1. Expression of p27and p18in human multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors

Author

Conemans, E B, Raicu-Ionita, G M, Pieterman, C R C, Dreijerink, K M A, Dekkers, O M, Hermus, A R, de Herder, W W, Drent, M L, van der Horst-Schrivers, A N A, Havekes, B, Bisschop, P H, Offerhaus, G J, Borel Rinkes, I H M, Valk, G D, Timmers, H Th M, Vriens, M R, Clinical Neuropsychology, and IBBA

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, endocrine system, endocrine system diseases, SDG 3 - Good Health and Well-being, Journal Article
Abstract

PURPOSE: Pancreatic neuroendocrine tumors are a major manifestation of multiple endocrine neoplasia type 1 (MEN1). This tumor syndrome is caused by germline mutations in MEN1, encoding menin. Insight into pathogenesis of these tumors might lead to new biomarkers and therapeutic targets for these patients. Several lines of evidence point towards a role for p27Kip1and p18Ink4cin MEN1-related tumor development in animal models for MEN1, but their contribution to human MEN1-related pancreatic neuroendocrine tumor development is not known.METHODS: In this study, we characterized protein expression of p27Kip1and p18Ink4cin human MEN1-related PanNETs by immunohistochemistry. From the nationwide DutchMEN1 Study Group database including > 90% of the Dutch MEN1 population, MEN1-patients, who underwent pancreatic surgery, were selected. A tissue micro-array was constructed with available paraffin tissue blocks, and PanNETs from 61 MEN1 patients were eligible for analysis.RESULTS: Expression of p27Kip1was high in 57 (93%) PanNETs and 67% of the tumors showed low expression of p18Ink4c(67.3%). No association was found between expression of either p27Kip1or p18Ink4cand clinic-pathological characteristics.CONCLUSIONS: These findings indicate that loss of p18Ink4c, but not p27Kip1, is a common event in the development of MEN1-related PanNETs. Restoration of p18Ink4cfunction through CDK4/6 inhibitors could be a therapeutic option for MEN1-related PanNETs.

Published
2018
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2. DNA methylation profiling in MEN1-related pancreatic neuroendocrine tumors reveals a potential epigenetic target for treatment

Author

Conemans, E B, primary, Lodewijk, L, additional, Moelans, C B, additional, Offerhaus, G J A, additional, Pieterman, C R C, additional, Morsink, F H, additional, Dekkers, O M, additional, de Herder, W W, additional, Hermus, A R, additional, van der Horst-Schrivers, A N, additional, Drent, M L, additional, Bisschop, P H, additional, Havekes, B, additional, Brosens, L A A, additional, Dreijerink, K M A, additional, Borel Rinkes, I H M, additional, Timmers, H Th M, additional, Valk, G D, additional, and Vriens, M R, additional

Published
2018
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3. DNA methylation profiling in MEN1-related pancreatic neuroendocrine tumors reveals a potential epigenetic target for treatment

Author

Conemans, E B, Lodewijk, L, Moelans, C B, Offerhaus, G J A, Pieterman, C R C, Morsink, F H, Dekkers, O M, de Herder, W W, Hermus, A R, van der Horst-Schrivers, A N, Drent, M L, Bisschop, P H, Havekes, B, Brosens, L A A, Dreijerink, K M A, Borel Rinkes, I H M, Timmers, H Th M, Valk, G D, Vriens, M R, Conemans, E B, Lodewijk, L, Moelans, C B, Offerhaus, G J A, Pieterman, C R C, Morsink, F H, Dekkers, O M, de Herder, W W, Hermus, A R, van der Horst-Schrivers, A N, Drent, M L, Bisschop, P H, Havekes, B, Brosens, L A A, Dreijerink, K M A, Borel Rinkes, I H M, Timmers, H Th M, Valk, G D, and Vriens, M R

Abstract

OBJECTIVE: Epigenetic changes contribute to pancreatic neuroendocrine tumor (PanNET) development. Hypermethylation of promoter DNA as a cause of tumor suppressor gene silencing is a well-established oncogenic mechanism that is potentially reversible and therefore an interesting therapeutic target. Multiple endocrine neoplasia type 1 (MEN1) is the most frequent cause of inherited PanNETs. The aim of this study was to determine promoter methylation profiles in MEN1-related PanNETs.DESIGN AND METHODS: Methylation-specific multiplex ligation-dependent probe amplification was used to assess promoter methylation of 56 tumor suppressor genes in MEN1-related (n = 61) and sporadic (n = 34) PanNETs. Differences in cumulative methylation index (CMI), individual methylation percentages and frequency of promoter hypermethylation between subgroups were analyzed.RESULTS: We found promoter methylation of a large number of potential tumor suppressor genes. CMI (median CMI: 912 vs 876, P = 0.207) was the same in MEN1-related and sporadic PanNETs. We found higher methylation percentages of CASP8 in MEN1-related PanNETs (median: 59% vs 16.5%, P = 0.002). In MEN1-related non-functioning PanNETs, the CMI was higher in larger PanNETs (>2 cm) (median: 969.5 vs 838.5; P = 0.021) and in PanNETs with liver metastases (median: 1036 vs 869; P = 0.013). Hypermethylation of MGMT2 was more frequent in non-functioning PanNETs compared to insulinomas (median: 44.7% vs 8.3%; P = 0.022). Hypermethylation of the Von Hippel-Lindau gene promoter was observed in one MEN1-related PanNET and was associated with loss of protein expression.CONCLUSION: Promoter hypermethylation is a frequent event in MEN1-related and sporadic PanNETs. Targeting DNA methylation could be of therapeutic value in MEN1 patients with advanced PanNETs.

Published
2018
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4. Expression of p27 Kip1 and p18 Ink4c in human multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors

Author

Conemans, E B, Raicu-Ionita, G M, Pieterman, C R C, Dreijerink, K M A, Dekkers, O M, Hermus, A R, de Herder, W W, Drent, M L, van der Horst-Schrivers, A N A, Havekes, B, Bisschop, P H, Offerhaus, G J, Borel Rinkes, I H M, Valk, G D, Timmers, H Th M, Vriens, M R, Conemans, E B, Raicu-Ionita, G M, Pieterman, C R C, Dreijerink, K M A, Dekkers, O M, Hermus, A R, de Herder, W W, Drent, M L, van der Horst-Schrivers, A N A, Havekes, B, Bisschop, P H, Offerhaus, G J, Borel Rinkes, I H M, Valk, G D, Timmers, H Th M, and Vriens, M R

Abstract

PURPOSE: Pancreatic neuroendocrine tumors are a major manifestation of multiple endocrine neoplasia type 1 (MEN1). This tumor syndrome is caused by germline mutations in MEN1, encoding menin. Insight into pathogenesis of these tumors might lead to new biomarkers and therapeutic targets for these patients. Several lines of evidence point towards a role for p27Kip1and p18Ink4cin MEN1-related tumor development in animal models for MEN1, but their contribution to human MEN1-related pancreatic neuroendocrine tumor development is not known.METHODS: In this study, we characterized protein expression of p27Kip1and p18Ink4cin human MEN1-related PanNETs by immunohistochemistry. From the nationwide DutchMEN1 Study Group database including > 90% of the Dutch MEN1 population, MEN1-patients, who underwent pancreatic surgery, were selected. A tissue micro-array was constructed with available paraffin tissue blocks, and PanNETs from 61 MEN1 patients were eligible for analysis.RESULTS: Expression of p27Kip1was high in 57 (93%) PanNETs and 67% of the tumors showed low expression of p18Ink4c(67.3%). No association was found between expression of either p27Kip1or p18Ink4cand clinic-pathological characteristics.CONCLUSIONS: These findings indicate that loss of p18Ink4c, but not p27Kip1, is a common event in the development of MEN1-related PanNETs. Restoration of p18Ink4cfunction through CDK4/6 inhibitors could be a therapeutic option for MEN1-related PanNETs.

Published
2018
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5. Expression of p27Kip1 and p18Ink4c in human multiple endocrine neoplasia type 1-related pancreatic neuroendocrine tumors

Author

Conemans, E. B., primary, Raicu-Ionita, G. M., additional, Pieterman, C. R. C., additional, Dreijerink, K. M. A., additional, Dekkers, O. M., additional, Hermus, A. R., additional, de Herder, W. W., additional, Drent, M. L., additional, van der Horst-Schrivers, A. N. A., additional, Havekes, B., additional, Bisschop, P. H., additional, Offerhaus, G. J., additional, Borel Rinkes, I. H. M., additional, Valk, G. D., additional, Timmers, H. Th. M., additional, and Vriens, M. R., additional

Published
2017
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8. Cognitive performance in older males is associated with growth hormone secretion.

Author

Quik EH, Conemans EB, Valk GD, Kenemans JL, Koppeschaar HP, and van Dam PS

Subjects
Aged, Cerebral Cortex metabolism, Cognition Disorders metabolism, Human Growth Hormone deficiency, Humans, Male, Middle Aged, Neuropsychological Tests, Aging physiology, Cerebral Cortex physiopathology, Cognition Disorders physiopathology, Human Growth Hormone metabolism
Abstract

Decreases in GH secretion with age may contribute to cognitive changes associated with aging. We evaluated the relation between GH secretion and cognition in elderly males by assessing correlations between GH secretion and performance on cognitive tests in conjunction with recording of event-related potentials (ERPs) to assess underlying neurophysiological mechanisms. GH secretion of 17 elderly male participants was assessed by a GHRH-GHRP-6 test. Standardized neuropsychological tests were used to assess cognitive function. EEG/ERPs were recorded to assess on-line electrocortical correlates of sensory-cortical processing and selective attention. GH secretion was significantly correlated with target detections and speed of responding in the selection-potential task. Furthermore, GH peak was significantly correlated with the performance letter-digit span test. The present data confirm that cognitive performance in elderly males is associated with GH secretion, with respect to target detection and speed of responding in conditions of selective attention, short-term memory, and basic processing speed., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Published
2012
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