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Girish Dhall - One of the best experts on this subject based on the ideXlab platform.
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Epigenetics impacts upon prognosis and clinical management of Choroid plexus tumors
Journal of Neuro-Oncology, 2020Co-Authors: Christian Thomas, Katie Metrock, Uwe Kordes, Martin Hasselblatt, Girish DhallAbstract:Purpose Choroid plexus tumors comprise of Choroid plexus papilloma (CPP, WHO grade I), atypical Choroid plexus papilloma (aCPP, WHO grade II) and Choroid plexus carcinoma (CPC, WHO grade III). Molecular events driving the majority of Choroid plexus tumors remain poorly understood. Recently, DNA methylation profiling has revealed different epigenetic subgroups. Methods Comprehensive review of epigenetic profiles of Choroid plexus tumors in the context of histopathological, genetic, and clinical features. Summary DNA methylation profiling segregates Choroid plexus tumors into three distinct epigenetic subgroups: supratentorial pediatric low-risk Choroid plexus tumors (CPP and aCPP), infratentorial adult low-risk Choroid plexus tumors (CPP and aCPP), and supratentorial pediatric high-risk Choroid plexus tumors (CPP and aCPP and CPC). Epigenetic subgrouping provides additional prognostic information in comparison to histopathological grading. Conclusions Epigenetic profiling of Choroid plexus tumors can be used for the identification of patients at risk of recurrence and is expected to play a role for treatment stratification and patient management in the context of future clinical trials.
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Epigenetics impacts upon prognosis and clinical management of Choroid plexus tumors
Journal of Neuro-Oncology, 2020Co-Authors: Christian Thomas, Katie Metrock, Uwe Kordes, Martin Hasselblatt, Girish DhallAbstract:Purpose Choroid plexus tumors comprise of Choroid plexus papilloma (CPP, WHO grade I), atypical Choroid plexus papilloma (aCPP, WHO grade II) and Choroid plexus carcinoma (CPC, WHO grade III). Molecular events driving the majority of Choroid plexus tumors remain poorly understood. Recently, DNA methylation profiling has revealed different epigenetic subgroups. Methods Comprehensive review of epigenetic profiles of Choroid plexus tumors in the context of histopathological, genetic, and clinical features. Summary DNA methylation profiling segregates Choroid plexus tumors into three distinct epigenetic subgroups: supratentorial pediatric low-risk Choroid plexus tumors (CPP and aCPP), infratentorial adult low-risk Choroid plexus tumors (CPP and aCPP), and supratentorial pediatric high-risk Choroid plexus tumors (CPP and aCPP and CPC). Epigenetic subgrouping provides additional prognostic information in comparison to histopathological grading. Conclusions Epigenetic profiling of Choroid plexus tumors can be used for the identification of patients at risk of recurrence and is expected to play a role for treatment stratification and patient management in the context of future clinical trials.
Werner Paulus - One of the best experts on this subject based on the ideXlab platform.
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Choroid plexus biology and pathology
Acta Neuropathologica, 2010Co-Authors: Hartwig Wolburg, Werner PaulusAbstract:The Choroid plexus is an epithelial–endothelial vascular convolute within the ventricular system of the vertebrate brain. It consists of epithelial cells, fenestrated blood vessels, and the stroma, dependent on various physiological or pathological conditions, which may contain fibroblasts, mast cells, macrophages, granulocytes or other infiltrates, and a rich extracellular matrix. The Choroid plexus is mainly involved in the production of cerebrospinal fluid (CSF) by using the free access to the blood compartment of the leaky vessels. In order to separate blood and CSF compartments, Choroid plexus epithelial cells and tanycytes of circumventricular organs constitute the blood–CSF–brain barrier. As non-neuronal cells in the brain and derived from neuroectoderm, Choroid plexus epithelia are defined as a subtype of macroglia. The Choroid plexus is involved in a variety of neurological disorders, including neurodegenerative, inflammatory, infectious, traumatic, neoplastic, and systemic diseases. Aβ and Biondi ring tangles accumulate in the Alzheimer’s disease Choroid plexus. In multiple sclerosis, the Choroid plexus could represent a site for lymphocyte entry in the CSF and brain, and for presentation of antigens. Recent studies have provided new diagnostic markers and potential molecular targets for Choroid plexus papilloma and carcinoma, which represent the most common brain tumors in the first year of life. We here revive some of the classical studies and review recent insight into the biology and pathology of the Choroid plexus.
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Malignant progression in Choroid plexus papillomas.
Journal of Neurosurgery, 2007Co-Authors: Astrid Jeibmann, Johannes E A Wolff, Werner Paulus, Brigitte Wrede, Ove Peters, Martin HasselblattAbstract:Object Malignant progression of Choroid plexus papillomas has been occasionally reported, but this issue has not yet been systematically addressed. Methods Frequency and extent of malignant progression were examined in a retrospective series of 124 primary Choroid plexus papillomas using uniform histological criteria. Results After gross-total resection and a mean follow-up period of 59 months, 12 recurrences necessitating neuro-surgical intervention had occurred in the 103 cases of Choroid plexus papilloma (World Health Organization [WHO] Grade I) and 21 cases of atypical Choroid plexus papilloma (WHO Grade II). The proportion of recurring tumors was higher in cases of atypical Choroid plexus papilloma than in cases of Choroid plexus papilloma (six [29%] of 21 compared with six [6%] of 103, respectively; p < 0.05). In the majority (10 of 12) of the recurrences, there was a close correspondence between the primary tumor and the recurrence with respect to features identified on routine histological examina...
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Malignant progression in Choroid plexus papillomas.
Journal of neurosurgery, 2007Co-Authors: Astrid Jeibmann, Johannes E A Wolff, Werner Paulus, Brigitte Wrede, Ove Peters, Martin HasselblattAbstract:Malignant progression of Choroid plexus papillomas has been occasionally reported, but this issue has not yet been systematically addressed. Frequency and extent of malignant progression were examined in a retrospective series of 124 primary Choroid plexus papillomas using uniform histological criteria. After gross-total resection and a mean follow-up period of 59 months, 12 recurrences necessitating neurosurgical intervention had occurred in the 103 cases of Choroid plexus papilloma (World Health Organization [WHO] Grade I) and 21 cases of atypical Choroid plexus papilloma (WHO Grade II). The proportion of recurring tumors was higher in cases of atypical Choroid plexus papilloma than in cases of Choroid plexus papilloma (six [29%] of 21 compared with six [6%] of 103, respectively; p < 0.05). In the majority (10 of 12) of the recurrences, there was a close correspondence between the primary tumor and the recurrence with respect to features identified on routine histological examination as well as Ki 67 (MIB-1) proliferation indices (median value 4% for both primary and recurrent tumors; range 0-15% for primary compared with 0-12% for recurrent tumors). However, two patients experienced a transition from a Choroid plexus papilloma (WHO Grade I) and an atypical Choroid plexus papilloma (WHO Grade II) to Choroid plexus carcinomas (WHO Grade III). Recurrent tumor growth after gross-total resection is rare in Choroid plexus papillomas, but malignant progression to Choroid plexus carcinoma does occur in a small percentage of tumors.
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Chromosomal imbalances in Choroid plexus tumors.
American Journal of Pathology, 2002Co-Authors: Christian H. Rickert, Otmar D. Wiestler, Werner PaulusAbstract:We studied 49 Choroid plexus tumors by comparative genomic hybridization. Chromosomal imbalances were found in 32 of 34 Choroid plexus papillomas and 15 of 15 Choroid plexus carcinomas. Choroid plexus papillomas frequently showed +7q (65%), +5q (62%), +7p (59%), +5p (56%), +9p (50%), +9q (41%), +12p, +12q (38%), and +8q (35%) as well as −10q (56%), −10p, and −22q (47%); Choroid plexus carcinomas mainly showed +12p, +12q, +20p (60%), +1, +4q, +20q (53%), +4p (47%), +8q, +14q (40%), +7q, +9p, +21 (33%) as well as −22q (73%), −5q (40%), −5p, and −18q (33%). Several chromosomal imbalance differences could be found that were characteristic for a tumor entity or age group. In Choroid plexus papillomas +5q, +6q, +7q, +9q, +15q, +18q, and −21q were significantly more common whereas Choroid plexus carcinomas were characterized by +1, +4q, +10, +14q, +20q, +21q, −5q, −9p, −11, −15q, and −18q. Among Choroid plexus papillomas, children more often showed +8q, +14q, +12, and +20q; adults mainly presented with +5q, +6q, +15q, +18q, and −22q. Although the number of aberrations overall as well as of gains and losses on their own bore no significance on survival among Choroid plexus tumors, a significantly longer survival among patients with Choroid plexus carcinomas was associated with +9p and −10q. Our results show that aberrations differ between Choroid plexus papillomas and Choroid plexus carcinomas as well as between pediatric and adult Choroid plexus papillomas, supporting the notion of different genetic pathways. Furthermore, gain of 9p and loss of 10q seem to be correlated with a more favorable prognosis in Choroid plexus carcinomas.
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Tumors of the Choroid plexus
Microscopy Research and Technique, 2001Co-Authors: Christian H. Rickert, Werner PaulusAbstract:Choroid plexus tumors are rare intraventricular papillary neoplasms derived from Choroid plexus epithelium, which account for only between 0.4–0.6% of all intracranial and 2–3% of pediatric neoplasms. Plexus papillomas outnumber Choroid plexus carcinomas by a ratio of 5:1 and around 80% of Choroid plexus carcinomas arise in children. Plexus tumors are most common in the lateral and fourth ventricles; while 80% of lateral ventricle tumors present in children, fourth ventricle tumors are evenly distributed in all age groups. Clinically, Choroid plexus tumors tend to cause hydrocephalus and increased intracranial pressure. Histologically, Choroid plexus papillomas correspond to WHO grade I, Choroid plexus carcinomas to WHO grade III. Immunohistochemically, cytokeratins and vimentin are expressed by virtually all Choroid plexus papillomas and most Choroid plexus carcinomas while transthyretin and S-100 protein are present in 80–90% of cases, less frequently, though, in Choroid plexus carcinomas. Glial fibrillary acidic protein can be found focally in about 25–55% of Choroid plexus papillomas and 20% of Choroid plexus carcinomas. The mean Ki67/MIB1 labeling index for Choroid plexus papillomas is 1.9%, for Choroid plexus carcinomas 13.8%. Choroid plexus papillomas typically show hyperdiploidy with gains particularly on chromosomes 7, 9, 12, 15, 17, and 18 while one Choroid plexus carcinoma showed rearrangements of chromosomes 7p11-12, 9q11-12, 15q22, and 19q13.4. Choroid plexus papillomas can usually be cured by surgery alone with a 5-year survival rate of up to 100% with occasional recurrences while Choroid plexus carcinomas grow more rapidly and have a less favorable outcome with a 5-year survival rate of 26–40%. Microsc. Res. Tech. 52:104–111, 2001. © 2001 Wiley-Liss, Inc.
Johannes E A Wolff - One of the best experts on this subject based on the ideXlab platform.
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Histone acetylation resulting in resistance to methotrexate in Choroid plexus cells
Journal of Neuro-Oncology, 2008Co-Authors: Preethi Prasad, Hernan Vasquez, Vidya Gopalakrishnan, Johannes E A WolffAbstract:Choroid plexus carcinomas are rare tumors that typically occur in young children. Prognosis is poor, and very little information is available to optimize treatment protocols. We used a cell culture model to evaluate whether combining chemotherapeutic agents such as methotrexate with histone deacetylase inhibitors (HDACI) such as valproic acid and MS-275 could improve efficacy. Valproic acid increased the cytotoxicity of radiation and of all the chemotherapeutic agents in Z310 and SV11 mouse Choroid plexus cell lines, with the exception of methotrexate. Both HDACIs made Choroid plexus cells resistant to this folate antagonist. Searching for a molecular explanation, we found that thymidylate synthase was up regulated when the cells were incubated with HDACI. We also confirmed this finding in human Choroid plexus carcinoma cells. Methotrexate should not be combined with HDACI in the treatment of Choroid plexus carcinoma.
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Malignant progression in Choroid plexus papillomas.
Journal of Neurosurgery, 2007Co-Authors: Astrid Jeibmann, Johannes E A Wolff, Werner Paulus, Brigitte Wrede, Ove Peters, Martin HasselblattAbstract:Object Malignant progression of Choroid plexus papillomas has been occasionally reported, but this issue has not yet been systematically addressed. Methods Frequency and extent of malignant progression were examined in a retrospective series of 124 primary Choroid plexus papillomas using uniform histological criteria. Results After gross-total resection and a mean follow-up period of 59 months, 12 recurrences necessitating neuro-surgical intervention had occurred in the 103 cases of Choroid plexus papilloma (World Health Organization [WHO] Grade I) and 21 cases of atypical Choroid plexus papilloma (WHO Grade II). The proportion of recurring tumors was higher in cases of atypical Choroid plexus papilloma than in cases of Choroid plexus papilloma (six [29%] of 21 compared with six [6%] of 103, respectively; p < 0.05). In the majority (10 of 12) of the recurrences, there was a close correspondence between the primary tumor and the recurrence with respect to features identified on routine histological examina...
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Malignant progression in Choroid plexus papillomas.
Journal of neurosurgery, 2007Co-Authors: Astrid Jeibmann, Johannes E A Wolff, Werner Paulus, Brigitte Wrede, Ove Peters, Martin HasselblattAbstract:Malignant progression of Choroid plexus papillomas has been occasionally reported, but this issue has not yet been systematically addressed. Frequency and extent of malignant progression were examined in a retrospective series of 124 primary Choroid plexus papillomas using uniform histological criteria. After gross-total resection and a mean follow-up period of 59 months, 12 recurrences necessitating neurosurgical intervention had occurred in the 103 cases of Choroid plexus papilloma (World Health Organization [WHO] Grade I) and 21 cases of atypical Choroid plexus papilloma (WHO Grade II). The proportion of recurring tumors was higher in cases of atypical Choroid plexus papilloma than in cases of Choroid plexus papilloma (six [29%] of 21 compared with six [6%] of 103, respectively; p < 0.05). In the majority (10 of 12) of the recurrences, there was a close correspondence between the primary tumor and the recurrence with respect to features identified on routine histological examination as well as Ki 67 (MIB-1) proliferation indices (median value 4% for both primary and recurrent tumors; range 0-15% for primary compared with 0-12% for recurrent tumors). However, two patients experienced a transition from a Choroid plexus papilloma (WHO Grade I) and an atypical Choroid plexus papilloma (WHO Grade II) to Choroid plexus carcinomas (WHO Grade III). Recurrent tumor growth after gross-total resection is rare in Choroid plexus papillomas, but malignant progression to Choroid plexus carcinoma does occur in a small percentage of tumors.
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Choroid plexus tumours
British Journal of Cancer, 2002Co-Authors: Johannes E A Wolff, Mitra Sajedi, Max J. Coppes, Rollin Brant, R. Maarten EgelerAbstract:Choroid plexus tumours are rare epithelial brain tumours and limited information is available regarding their biology and the best treatment. A meta-analysis was done to determine prognostic factors and the influence of various treatment modalities. A thorough review of the medical literature (1966–1998) revealed 566 well-documented Choroid plexus tumours. These were entered into a database, which was analysed to determine prognostic factors and treatment modalities. Most patients with a supratentorial tumour were children, while the most common sites in adults were the fourth ventricle and the cerebellar pontine angle. Cerebellar pontine angle tumours were more frequently benign. Histology was the most important prognostic factor, as one, five, and 10-year projected survival rates were 90, 81, and 77% in Choroid plexus-papilloma (n=353) compared to only 71, 41, and 35% in Choroid plexus-carcinoma respectively (P<0.0005). Surgery was prognostically relevant for both Choroid plexus-papilloma (P=0.0005) and Choroid plexus-carcinoma (P=0.0001). Radiotherapy was associated with significantly better survival in Choroid plexus-carcinomas. Eight of 22 documented Choroid plexus-carcinomas responded to chemotherapy. Relapse after primary treatment was a poor prognostic factor in Choroid plexus-carcinoma patients but not in Choroid plexus-papilloma patients. Treatment of Choroid plexus tumours should start with radical surgical resection. This should be followed by adjuvant treatment in case of Choroid plexus-carcinoma, and a ‘wait and see’ approach in Choroid plexus-papilloma. British Journal of Cancer (2002) 87, 1086–1091. doi:10.1038/sj.bjc.6600609 www.bjcancer.com © 2002 Cancer Research UK
Kevin F Chau - One of the best experts on this subject based on the ideXlab platform.
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mice expressing myc in neural precursors develop Choroid plexus and ciliary body tumors
American Journal of Pathology, 2018Co-Authors: Morgan L Shannon, Kevin F Chau, Ryann M Fame, Neil Dani, Monica L Calicchio, Gwenaelle S G Geleoc, Hart G W Lidov, Sanda Alexandrescu, Maria K LehtinenAbstract:Choroid plexus tumors and ciliary body medulloepithelioma are predominantly pediatric neoplasms. Progress in understanding the pathogenesis of these tumors has been hindered by their rarity and lack of models that faithfully recapitulate the disease. Here, we find that endogenous Myc proto-oncogene protein is down-regulated in the forebrain neuroepithelium, whose neural plate border domains give rise to the anterior Choroid plexus and ciliary body. To uncover the consequences of persistent Myc expression, MYC expression was forced in multipotent neural precursors (nestin-Cre:Myc), which produced fully penetrant models of Choroid plexus carcinoma and ciliary body medulloepithelioma. Nestin-mediated MYC expression in the epithelial cells of Choroid plexus leads to the regionalized formation of Choroid plexus carcinoma in the posterior domain of the lateral ventricle Choroid plexus and the fourth ventricle Choroid plexus that is accompanied by loss of multiple cilia, up-regulation of protein biosynthetic machinery, and hydrocephalus. Parallel MYC expression in the ciliary body leads also to up-regulation of protein biosynthetic machinery. Additionally, Myc expression in human Choroid plexus tumors increases with aggressiveness of disease. Collectively, our findings expose a select vulnerability of the neuroepithelial lineage to postnatal tumorigenesis and provide a new mouse model for investigating the pathogenesis of these rare pediatric neoplasms.
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spatially heterogeneous Choroid plexus transcriptomes encode positional identity and contribute to regional csf production
The Journal of Neuroscience, 2015Co-Authors: Matthew B Johnson, Momoko Watanabe, Kevin F Chau, Mark W Springel, Alexandra Malesz, Mihovil Pletikos, André M. M. Sousa, Youngjin Kang, Kevin G Broadbelt, Tai AdelitaAbstract:A sheet of Choroid plexus epithelial cells extends into each cerebral ventricle and secretes signaling factors into the CSF. To evaluate whether differences in the CSF proteome across ventricles arise, in part, from regional differences in Choroid plexus gene expression, we defined the transcriptome of lateral ventricle (telencephalic) versus fourth ventricle (hindbrain) Choroid plexus. We find that positional identities of mouse, macaque, and human Choroid plexi derive from gene expression domains that parallel their axial tissues of origin. We then show that molecular heterogeneity between telencephalic and hindbrain Choroid plexi contributes to region-specific, age-dependent protein secretion in vitro. Transcriptome analysis of FACS-purified Choroid plexus epithelial cells also predicts their cell-type-specific secretome. Spatial domains with distinct protein expression profiles were observed within each Choroid plexus. We propose that regional differences between Choroid plexi contribute to dynamic signaling gradients across the mammalian cerebroventricular system.
Maria K Lehtinen - One of the best experts on this subject based on the ideXlab platform.
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mice expressing myc in neural precursors develop Choroid plexus and ciliary body tumors
American Journal of Pathology, 2018Co-Authors: Morgan L Shannon, Kevin F Chau, Ryann M Fame, Neil Dani, Monica L Calicchio, Gwenaelle S G Geleoc, Hart G W Lidov, Sanda Alexandrescu, Maria K LehtinenAbstract:Choroid plexus tumors and ciliary body medulloepithelioma are predominantly pediatric neoplasms. Progress in understanding the pathogenesis of these tumors has been hindered by their rarity and lack of models that faithfully recapitulate the disease. Here, we find that endogenous Myc proto-oncogene protein is down-regulated in the forebrain neuroepithelium, whose neural plate border domains give rise to the anterior Choroid plexus and ciliary body. To uncover the consequences of persistent Myc expression, MYC expression was forced in multipotent neural precursors (nestin-Cre:Myc), which produced fully penetrant models of Choroid plexus carcinoma and ciliary body medulloepithelioma. Nestin-mediated MYC expression in the epithelial cells of Choroid plexus leads to the regionalized formation of Choroid plexus carcinoma in the posterior domain of the lateral ventricle Choroid plexus and the fourth ventricle Choroid plexus that is accompanied by loss of multiple cilia, up-regulation of protein biosynthetic machinery, and hydrocephalus. Parallel MYC expression in the ciliary body leads also to up-regulation of protein biosynthetic machinery. Additionally, Myc expression in human Choroid plexus tumors increases with aggressiveness of disease. Collectively, our findings expose a select vulnerability of the neuroepithelial lineage to postnatal tumorigenesis and provide a new mouse model for investigating the pathogenesis of these rare pediatric neoplasms.
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enlargement of Choroid plexus in complex regional pain syndrome
Scientific Reports, 2015Co-Authors: Guangyu Zhou, Maria K Lehtinen, Jaakko Hotta, Nina Forss, Riitta HariAbstract:The Choroid plexus, located in brain ventricles, has received surprisingly little attention in clinical neuroscience. In morphometric brain analysis, we serendipitously found a 21% increase in Choroid plexus volume in 12 patients suffering from complex regional pain syndrome (CRPS) compared with age- and gender-matched healthy subjects. No enlargement was observed in a group of 8 patients suffering from chronic pain of other etiologies. Our findings suggest involvement of the Choroid plexus in the pathogenesis of CRPS. Since the Choroid plexus can mediate interaction between peripheral and brain inflammation, our findings pinpoint the Choroid plexus as an important target for future research of central pain mechanisms.