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Article ; Online: Targeting protein folding in N-Myc-driven medulloblastoma.

Valinciute, Gintvile / Roussel, Martine F

2023 Volume 17, Issue 3, Page(s) 387–389

Abstract: Selective targeting of N-Myc-driven Sonic hedgehog (SHH) medulloblastoma has been a challenge for many years and, despite decades of research, few targeted therapy opportunities exist. Recently, Kuzuoglu-Ozturk et al. characterized the translatome of N- ... ...

Abstract	Selective targeting of N-Myc-driven Sonic hedgehog (SHH) medulloblastoma has been a challenge for many years and, despite decades of research, few targeted therapy opportunities exist. Recently, Kuzuoglu-Ozturk et al. characterized the translatome of N-Myc-driven medulloblastoma as a promising therapeutic target. The study showed that N-Myc controls a subset of members of the protein folding machinery that could be inhibited pharmacologically and validated a subset of Hsp70 functions as required for medulloblastoma progression in vitro and in vivo.
MeSH term(s)	Humans ; Cerebellar Neoplasms/genetics ; Cerebellar Neoplasms/metabolism ; Hedgehog Proteins/metabolism ; Medulloblastoma/genetics ; Medulloblastoma/metabolism ; Protein Folding ; Signal Transduction ; N-Myc Proto-Oncogene Protein/metabolism
Chemical Substances	Hedgehog Proteins ; N-Myc Proto-Oncogene Protein
Language	English
Publishing date	2023-02-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13395
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Article ; Online: Modeling pediatric medulloblastoma.

Roussel, Martine F / Stripay, Jennifer L

Brain pathology (Zurich, Switzerland)

2019 Volume 30, Issue 3, Page(s) 703–712

Abstract: Mouse models of medulloblastoma have proven to be instrumental in understanding disease mechanisms, particularly the role of epigenetic and molecular drivers, and establishing appropriate preclinical pipelines. To date, our research community has ... ...

Abstract	Mouse models of medulloblastoma have proven to be instrumental in understanding disease mechanisms, particularly the role of epigenetic and molecular drivers, and establishing appropriate preclinical pipelines. To date, our research community has developed murine models for all four groups of medulloblastoma, each of which will be critical for the identification and development of new therapeutic approaches. Approaches to modeling medulloblastoma range from genetic engineering with CRISPR/Cas9 or in utero electroporation, to orthotopic and patient-derived orthotopic xenograft systems. Each approach or model presents unique advantages that have ultimately contributed to an appreciation of medulloblastoma heterogeneity and the clinical obstacles that exist for this patient population.
MeSH term(s)	Animals ; Cell Line, Tumor ; Cerebellar Neoplasms/pathology ; Disease Models, Animal ; Medulloblastoma/pathology ; Mice
Language	English
Publishing date	2019-12-17
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1051484-3
ISSN	1750-3639 ; 1015-6305
ISSN (online)	1750-3639
ISSN	1015-6305
DOI	10.1111/bpa.12803
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Zs.A 3585: Show issues

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Article: Preclinical Models of Craniospinal Irradiation for Medulloblastoma.

Stripay, Jennifer L / Merchant, Thomas E / Roussel, Martine F / Tinkle, Christopher L

Cancers

2020 Volume 12, Issue 1

Abstract: ...

Abstract	:
Language	English
Publishing date	2020-01-05
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers12010133
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Article ; Online: Epigenetic Drivers in Pediatric Medulloblastoma.

Roussel, Martine F / Stripay, Jennifer L

Cerebellum (London, England)

2017 Volume 17, Issue 1, Page(s) 28–36

Abstract: Epigenetics is the process by which gene expression is regulated by events other than alterations of the genome. This includes DNA methylation, histone modifications, chromatin remodeling, microRNAs, and long non-coding RNAs. Methylation of DNA, ... ...

Abstract	Epigenetics is the process by which gene expression is regulated by events other than alterations of the genome. This includes DNA methylation, histone modifications, chromatin remodeling, microRNAs, and long non-coding RNAs. Methylation of DNA, chromatin remodeling, and histone modifications regulate the chromatin and access of transcription factors to DNA and in turn gene transcription. Alteration of chromatin is now recognized to be deregulated in many cancers. Medulloblastoma is an embryonal tumor of the cerebellum and the most common malignant brain tumor in children, that occurs only rarely in adults. Medulloblastoma is characterized by four major molecularly and histopathologically distinct groups, wingless (WNT), sonic hedgehog (SHH), group 3 (G3), and group 4 (G4), that, except for WNT, are each now subdivided in several subgroups. Gene expression array, next-generation sequencing, and methylation profiling of several hundred primary tumors by several consortia and independent groups revealed that medulloblastomas harbor a paucity of mutations most of which occur in epigenetic regulators, genetic alterations in oncogenes and tumor suppressors, in addition to copy number alterations and chromosome gains and losses. Remarkably, some tumors have no reported mutations, suggesting that some genes required for oncogenesis might be regulated by epigenetic mechanisms which are still to be uncovered and validated. This review will highlight several epigenetic regulators focusing mainly on histone modifiers identified in medulloblastoma.
MeSH term(s)	Cerebellar Neoplasms/genetics ; Cerebellar Neoplasms/metabolism ; Epigenomics/methods ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Medulloblastoma/genetics ; Medulloblastoma/metabolism ; Signal Transduction
Language	English
Publishing date	2017-11-24
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2112586-7
ISSN	1473-4230 ; 1473-4222
ISSN (online)	1473-4230
ISSN	1473-4222
DOI	10.1007/s12311-017-0899-9
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Zs.A 5795: Show issues

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Article ; Online: LC-MS/MS method for quantitation of gemcitabine and its metabolite 2',2'-difluoro-2'-deoxyuridine in mouse plasma and brain tissue: Application to a preclinical pharmacokinetic study.

Zhong, Bo / Gibson, Elizabeth G / Davis, Abi / Roussel, Martine F / Stewart, Clinton F

Journal of pharmaceutical and biomedical analysis

2021 Volume 198, Page(s) 114025

Abstract: A simple, sensitive, and relatively fast assay was developed and validated for the quantitation of gemcitabine (dFdC) and its major metabolite 2',2'-difluoro-2'-deoxyuridine (dFdU) in mouse plasma and brain tissue. The assay used a small sample (25 μL ... ...

Abstract	A simple, sensitive, and relatively fast assay was developed and validated for the quantitation of gemcitabine (dFdC) and its major metabolite 2',2'-difluoro-2'-deoxyuridine (dFdU) in mouse plasma and brain tissue. The assay used a small sample (25 μL plasma and 5 mg brain) for extraction by protein precipitation. After dilution of the supernatant extract, 1 μL was injected into HPLC system for reverse phase chromatographic separation with a total run time of 8 min. Chromatographic resolution of dFdC and dFdU was achieved on a Gemini C18 column (50 × 4.6 mm, 3 μm) utilizing gradient elution. Multiple reaction monitoring (MRM) with positive/negative ion switching was performed for detection of dFdC and its internal standard (dFdC-IS) in positive ion mode and dFdU and its IS (dFdU-IS) in negative ion mode. Two calibration curves ranging from 5-2000 ng/mL and 250-50,000 ng/mL were generated for dFdC and dFdU in mouse plasma, respectively. For measurement of dFdC and dFdU in mouse brain tissue, another two curves were used ranging from 0.02 to 40 ng/mg and 1-40 ng/mg, respectively. This assay demonstrated excellent precision and accuracy within day and between days for simultaneous measurement of dFdC and dFdU at all the concentration levels in both matrices. The other parameters such as selectivity, sensitivity, matrix effects, recovery, and storage stability were also assessed for both analytes in each matrix. Compared to the previously reported methods, the sample extraction in the current assay was simplified significantly, and the analysis time was greatly shortened. We successfully applied the validated method to the analysis of dFdC and dFdU in mouse plasma, brain, and brain tumor tissue in a preclinical pharmacokinetic study.
MeSH term(s)	Animals ; Brain ; Chromatography, High Pressure Liquid ; Chromatography, Liquid ; Deoxycytidine/analogs & derivatives ; Floxuridine/analogs & derivatives ; Mice ; Reproducibility of Results ; Tandem Mass Spectrometry
Chemical Substances	Floxuridine (039LU44I5M) ; Deoxycytidine (0W860991D6) ; gemcitabine (B76N6SBZ8R) ; 2',2'-difluoro-2'-deoxyuridine (Y30D8SIL1I)
Language	English
Publishing date	2021-03-13
Publishing country	England
Document type	Journal Article
ZDB-ID	604917-5
ISSN	1873-264X ; 0731-7085
ISSN (online)	1873-264X
ISSN	0731-7085
DOI	10.1016/j.jpba.2021.114025
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Zs.A 1850: Show issues

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Article ; Online: [No title information]

Coquelet, Amélie / Besozzi, Anaïck / Roussel, Martine / Lemetayer, Fabienne

Geriatrie et psychologie neuropsychiatrie du vieillissement

2022 Volume 20, Issue 1, Page(s) 79–95

Abstract: Résumé L'augmentation de l'espérance de vie des personnes porteuses d'une trisomie 21 (PPT21) s'accompagne de nouvelles problématiques telles que le déclin cognitif lié au vieillissement et le dépistage/diagnostic de la maladie d'Alzheimer (MA). À ... ...

Title translation	Évaluation neuropsychologique des adultes porteurs d’une trisomie 21 en Consultation mémoire : quels outils ? Une revue de la littérature.
Abstract	Résumé L'augmentation de l'espérance de vie des personnes porteuses d'une trisomie 21 (PPT21) s'accompagne de nouvelles problématiques telles que le déclin cognitif lié au vieillissement et le dépistage/diagnostic de la maladie d'Alzheimer (MA). À travers une revue de la littérature, cet article recense les principaux outils existants pour l'évaluation neuropsychologique de cette population. À partir des bases de données PsycINFO, PubMed, Web of Science, Wiley et le moteur de recherches Google Scholar, ont été inclus dans l'étude les articles publiés de juillet à décembre 2020, concernant les PPT21 d'âge supérieur ou égal à 18 ans et contenant des échelles d'évaluation cognitive. Quatre-vingt-cinq articles ont été sélectionnés qui comprenaient 186 outils d'évaluation. La quasi-totalité de ces épreuves n'a toutefois pas fait l'objet de validation en langue française et moins d'un tiers étaient spécifiquement conc¸us pour une évaluation diagnostique de la MA chez des PPT21. L'objectif de cette revue est de souligner la nécessité de développer des outils neuropsychologiques spécifiques pour le diagnostic de MA chez les PPT21, validés en langue française. Abstract Improvement of life expectancy in people with Down syndrome (DS) is associated with new problems such as cognitive decline associated with aging and screening/diagnosis for Alzheimer's disease (AD) in this population. The aim of this review is to identify the main tools used in the literature for the cognitive evaluation in this population. Research was conducted on PsycINFO, PubMed, Web of Science and Wiley databases and Google Scholar from July to November 2020, concerning persons with DS, aged of 18 years or more, and evaluated with cognitive assessment scales.196 assessment tools were identified among the 85 articles included. However, most tools had not been validated in French, and only one third were specifically designed for a diagnosis of AD in people with DS. These results underline the need to develop specific tools for the diagnosis of AD in people with DS and validated in French.
MeSH term(s)	Aged ; Aging ; Down Syndrome ; Humans ; Referral and Consultation ; Trisomy
Language	French
Publishing date	2022-06-02
Publishing country	France
Document type	Journal Article ; Review
ISSN	2115-7863
ISSN (online)	2115-7863
DOI	10.1684/pnv.2022.1025
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Article: CAR T-cell design dependent remodeling of the brain tumor immune microenvironment identify macrophages as key players that inhibit or promote anti-tumor activity.

Haydar, Dalia / Ibañez-Vega, Jorge / Crawford, Jeremy Chase / Chou, Ching-Heng / Guy, Cliff / Meehl, Michaela / Yi, Zhongzhen / Langfitt, Deanna / Vogel, Peter / DeRenzo, Christopher / Gottschalk, Stephen / Roussel, Martine F / Thomas, Paul G / Krenciute, Giedre

Research square

2023

Abstract: Understanding interactions between adoptively transferred immune cells and the tumor immune microenvironment (TIME) is critical for developing successful T-cell based immunotherapies. Here we investigated the impact of the TIME and chimeric antigen ... ...

Abstract	Understanding interactions between adoptively transferred immune cells and the tumor immune microenvironment (TIME) is critical for developing successful T-cell based immunotherapies. Here we investigated the impact of the TIME and chimeric antigen receptor (CAR) design on anti-glioma activity of B7-H3-specific CAR T-cells. We show that five out of six B7-H3 CARs with varying transmembrane, co-stimulatory, and activation domains, exhibit robust functionality
Language	English
Publishing date	2023-06-06
Publishing country	United States
Document type	Preprint
DOI	10.21203/rs.3.rs-2972427/v1
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Article ; Online ; Conference proceedings: New concepts in organ site research on medulloblastoma: genetics and genomics.

Roussel, Martine F

Future oncology (London, England)

2010 Volume 6, Issue 8, Page(s) 1229–1231

Abstract: Medulloblastoma is the most common solid tumor in childhood, developing in the cerebellum, a hindbrain structure with origins from two distinct germinal zones. Therefore, medulloblastoma tumors show a diversity of signaling abnormalities and stem cell ... ...

Abstract	Medulloblastoma is the most common solid tumor in childhood, developing in the cerebellum, a hindbrain structure with origins from two distinct germinal zones. Therefore, medulloblastoma tumors show a diversity of signaling abnormalities and stem cell biologies. Sonic Hedgehog and Wnt pathways drive a substantial fraction of tumors; however, genetic pathways underlying the most aggressive subset of these tumors remain uncharted. The speakers of this session discussed the genetic diversity of both tumors and metastases, including forward genetic screens, molecular classifications and stem cell biology. They also addressed novel signaling pathways, mouse models and biomarkers, and clinical progress in targeting inappropriate activation of Shh signaling.
MeSH term(s)	Animals ; Biomedical Research/trends ; Cerebellar Neoplasms/diagnosis ; Cerebellar Neoplasms/genetics ; Cerebellar Neoplasms/therapy ; Genomics ; Humans ; Medulloblastoma/diagnosis ; Medulloblastoma/genetics ; Medulloblastoma/therapy ; Mice ; Signal Transduction/genetics
Language	English
Publishing date	2010-08
Publishing country	England
Document type	Congresses ; Research Support, N.I.H., Extramural
ZDB-ID	2184533-5
ISSN	1744-8301 ; 1479-6694
ISSN (online)	1744-8301
ISSN	1479-6694
DOI	10.2217/fon.10.86
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Article ; Online: Women in cancer research.

Mitchell, Christina A / Roussel, Martine F / Walsh, Leonie / Weeraratna, Ashani T

Nature reviews. Cancer

2019 Volume 19, Issue 10, Page(s) 547–552

Abstract: Gender inequality in science is a real issue, and without frank and open discussions leading to positive action it is likely to remain so. In February 2019, Nature Reviews Cancer was kindly invited to be part of a 'Women in Science Mentoring' panel ... ...

Abstract	Gender inequality in science is a real issue, and without frank and open discussions leading to positive action it is likely to remain so. In February 2019, Nature Reviews Cancer was kindly invited to be part of a 'Women in Science Mentoring' panel discussion, which took place at the Lorne Cancer Conference in Victoria, Australia. Inspired by the scientific career paths and experiences of the women on the panel, we decided to share their stories with our readers in this Viewpoint article, along with their opinions on how men and women must equally take responsibility for supporting and empowering female scientists. To this end, we hope we might contribute in some small way to highlighting a few of the issues surrounding gender bias in cancer research, as well as science more generally, and show our commitment to ensuring gender diversity within the journal.
MeSH term(s)	Biomedical Research/organization & administration ; Congresses as Topic ; Female ; Humans ; Male ; Medical Oncology/methods ; Mentors ; Neoplasms/therapy ; Sexism ; Women, Working
Language	English
Publishing date	2019-08-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2062767-1
ISSN	1474-1768 ; 1474-175X
ISSN (online)	1474-1768
ISSN	1474-175X
DOI	10.1038/s41568-019-0176-y
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Zs.A 5563: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 24: Show issues

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Article ; Online: Group 3 medulloblastoma transcriptional networks collapse under domain specific EP300/CBP inhibition.

Nature communications

2024 Volume 15, Issue 1, Page(s) 3483

Abstract: Chemical discovery efforts commonly target individual protein domains. Many proteins, including the EP300/CBP histone acetyltransferases (HATs), contain several targetable domains. EP300/CBP are critical gene-regulatory targets in cancer, with existing ... ...

Abstract	Chemical discovery efforts commonly target individual protein domains. Many proteins, including the EP300/CBP histone acetyltransferases (HATs), contain several targetable domains. EP300/CBP are critical gene-regulatory targets in cancer, with existing high potency inhibitors of either the catalytic HAT domain or protein-binding bromodomain (BRD). A domain-specific inhibitory approach to multidomain-containing proteins may identify exceptional-responding tumor types, thereby expanding a therapeutic index. Here, we discover that targeting EP300/CBP using the domain-specific inhibitors, A485 (HAT) or CCS1477 (BRD) have different effects in select tumor types. Group 3 medulloblastoma (G3MB) cells are especially sensitive to BRD, compared with HAT inhibition. Structurally, these effects are mediated by the difluorophenyl group in the catalytic core of CCS1477. Mechanistically, bromodomain inhibition causes rapid disruption of genetic dependency networks that are required for G3MB growth. These studies provide a domain-specific structural foundation for drug discovery efforts targeting EP300/CBP and identify a selective role for the EP300/CBP bromodomain in maintaining genetic dependency networks in G3MB.
MeSH term(s)	Humans ; Medulloblastoma/genetics ; Medulloblastoma/drug therapy ; Medulloblastoma/metabolism ; Medulloblastoma/pathology ; E1A-Associated p300 Protein/metabolism ; E1A-Associated p300 Protein/genetics ; E1A-Associated p300 Protein/antagonists & inhibitors ; Cell Line, Tumor ; Gene Regulatory Networks/drug effects ; Animals ; Protein Domains ; Gene Expression Regulation, Neoplastic/drug effects ; Mice ; Cerebellar Neoplasms/genetics ; Cerebellar Neoplasms/drug therapy ; Cerebellar Neoplasms/metabolism ; Cerebellar Neoplasms/pathology ; Antineoplastic Agents/pharmacology
Chemical Substances	E1A-Associated p300 Protein (EC 2.3.1.48) ; EP300 protein, human (EC 2.3.1.48) ; Antineoplastic Agents
Language	English
Publishing date	2024-04-25
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-47102-0
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