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Article: DNA methylation-based diagnosis confirmation in a pediatric patient with low-grade glioma: a case report.

Morgacheva, Daria / Ryzhova, Marina / Zheludkova, Olga / Belogurova, Margarita / Dinikina, Yulia

2023 Volume 11, Page(s) 1256876

Abstract: Central nervous system (CNS) tumors in children comprise a highly heterogenous and complex group of diseases. Historically, diagnosis and confirmation of these tumors were routinely based on histological examination. However, recently obtained data ... ...

Abstract	Central nervous system (CNS) tumors in children comprise a highly heterogenous and complex group of diseases. Historically, diagnosis and confirmation of these tumors were routinely based on histological examination. However, recently obtained data demonstrate that such a diagnostic approach is not completely accurate and could lead to misdiagnosis. Also, in recent times, the quantity and quality of molecular diagnostic methods have greatly improved, which influences the current classification methods and treatment approach for pediatric CNS tumors. Nowadays, molecular methods, such as DNA methylation profiling, are an integral part of diagnosing brain and spinal tumors in children. In this paper, we present the case of an infant with a posterior fossa tumor who demonstrated a non-specific morphology and whose diagnosis was verified only after DNA methylation.
Language	English
Publishing date	2023-09-25
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2711999-3
ISSN	2296-2360
ISSN	2296-2360
DOI	10.3389/fped.2023.1256876
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Article: The Bi-(AID-1-T) G-Quadruplex Has a Janus Effect on Primary and Recurrent Gliomas: Anti-Proliferation and Pro-Migration.

Pavlova, Svetlana / Fab, Lika / Savchenko, Ekaterina / Ryabova, Anastasia / Ryzhova, Marina / Revishchin, Alexander / Pronin, Igor / Usachev, Dmitry / Kopylov, Alexey / Pavlova, Galina

Pharmaceuticals (Basel, Switzerland)

2024 Volume 17, Issue 1

Abstract: High-grade gliomas are considered an incurable disease. Despite all the various therapy options available, patient survival remains low, and the tumor usually returns. Tumor resistance to conventional therapy and stimulation of the migratory activity of ... ...

Abstract	High-grade gliomas are considered an incurable disease. Despite all the various therapy options available, patient survival remains low, and the tumor usually returns. Tumor resistance to conventional therapy and stimulation of the migratory activity of surviving cells are the main factors that lead to recurrent tumors. When developing new treatment approaches, the effect is most often evaluated on standard and phenotypically depleted cancer cell lines. Moreover, there is much focus on the anti-proliferative effect of such therapies without considering the possible stimulation of migratory activity. In this paper, we studied how glioma cell migration changes after exposure to bi-(AID-1-T), an anti-proliferative aptamer. We investigated the effect of this aptamer on eight human glioma cell cultures (Grades III and IV) that were derived from patients' tumor tissue; the difference between primary and recurrent tumors was taken into account. Despite its strong anti-proliferative activity, bi-(AID-1-T) was shown to induce migration of recurrent tumor cells. This result shows the importance of studying the effect of therapeutic molecules on the invasive properties of glioma tumor cells in order to reduce the likelihood of inducing tumor recurrence.
Language	English
Publishing date	2024-01-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2193542-7
ISSN	1424-8247
ISSN	1424-8247
DOI	10.3390/ph17010074
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Article: Medulloblastomas in Pediatric and Adults.

Gorelyshev, Sergey / Medvedeva, Olga / Mazerkina, Nadezhda / Ryzhova, Marina / Krotkova, Olga / Golanov, Andrey

Advances in experimental medicine and biology

2023 Volume 1405, Page(s) 117–152

Abstract: Medulloblastoma is the primary malignant embryonic tumor of the cerebellum and the most common malignant tumor of childhood, accounting up to 25% of all CNS tumors in children, but is extremely rare in adults. Despite the fact that medulloblastomas are ... ...

Abstract	Medulloblastoma is the primary malignant embryonic tumor of the cerebellum and the most common malignant tumor of childhood, accounting up to 25% of all CNS tumors in children, but is extremely rare in adults. Despite the fact that medulloblastomas are one of the most malignant human tumors, it is worthy to note that a great breakthrough has been achieved in our understanding of oncogenesis and the development of real methods of treatment. The main objective of surgical treatment is a maximum resection of tumor with minimal impairment of neurological functions, in order to reduce the volume, remove tumor tissue, get the biopsy, and restore the cerebrospinal fluid flow. The progress of surgical techniques (using a microscope, ultrasound suction), anesthesiology, and intensive care has significantly decreased surgical mortality and increased radicality of tumor removal. Postoperative mortality is less than one percent in most studies, while neurological complications have been reported between 5-10%. Radiotherapy is the main method of treatment in patients older than 3 years, which dramatically improved the recurrence-free survival. Nevertheless, the radiation therapy without systemic chemotherapy leads to a high risk of systemic metastases. After the role of chemotherapy was statistically proven, investigations of the optimal combination of different chemotherapy regimens continued around the world. Currently, 80% of patients can already be cured, however, the quality of life of patients in the long-term period remains quite low, which depends on many factors including endocrinological, cognitive, neurological, and otoneurologic aspects. Thus, the main strategic goal of the development of neuro-oncology is to reduce the doses of radiation therapy to the CNS and the main task of international research is to optimize existing protocols and develop fundamentally new ones based on molecular genetic research in order to improve the quality of life.
MeSH term(s)	Child ; Humans ; Adult ; Medulloblastoma/therapy ; Quality of Life ; Combined Modality Therapy ; Antineoplastic Combined Chemotherapy Protocols ; Cerebellar Neoplasms/drug therapy ; Cerebellar Neoplasms/radiotherapy
Language	English
Publishing date	2023-07-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	410187-X
ISSN	0065-2598
ISSN	0065-2598
DOI	10.1007/978-3-031-23705-8_5
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Zs.A 3192: 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)
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Article ; Online: Cerebellar anaplastic astrocytoma in adult patients: 15 consecutive cases from a single institution and literature review.

Belyaev, Artem / Usachev, Dmitry / Ryzhova, Marina / Gulida, Gleb / Skvortsova, Vasilisa / Pronin, Igor / Kobiakov, Grigory

Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia

2021 Volume 91, Page(s) 249–254

Abstract: Adult cerebellar anaplastic astrocytomas (cAA) are rare entities and their clinical and genetic appearances are still ill defined. Previously, malignant gliomas of the cerebellum were combined and reviewed together (cAA and cerebellar glioblastomas (cGB), ...

Abstract	Adult cerebellar anaplastic astrocytomas (cAA) are rare entities and their clinical and genetic appearances are still ill defined. Previously, malignant gliomas of the cerebellum were combined and reviewed together (cAA and cerebellar glioblastomas (cGB), that could have possibly affected overall survival (OS) and progression-free survival (PFS). We present characteristics of 15 adult patients with cAA and compared them to a series of 45 patients with a supratentorial AA (sAA) in order to elicit the effect of tumor location on OS and PFS. The mean age at cAA diagnosis was 39.3 years (range 19-72). A history of neurofibromatosis type I was noted in 1 patient (6.7%). An IDH-1 mutation was identified in 6/15 cases and a methylated MGMT promoter in 5/15 cases. Patients in study and control groups were matched in age, sex and IDH-1 mutation status. Patients in a study group tended to present with longer overall survival (50 vs. 36.5 months), but the difference did not reach statistical significance. In both cAA and supratentorial AA groups presence of the IDH-1 mutation remains a positive predictor for the prolonged survival. The present study suggests that adult cAA constitute a group of gliomas with relatively higher rate of IDH-1 mutations and prognosis similar to supratentorial AA. The present study is the first to systematically compare cAA and supratentorial AA with respect to their genetic characteristics and suggests that both groups show a similar survival prognosis.
MeSH term(s)	Adult ; Aged ; Astrocytoma ; Brain Neoplasms/genetics ; Brain Neoplasms/therapy ; Humans ; Isocitrate Dehydrogenase/genetics ; Middle Aged ; Mutation ; Prognosis ; Young Adult
Chemical Substances	Isocitrate Dehydrogenase (EC 1.1.1.41)
Language	English
Publishing date	2021-07-22
Publishing country	Scotland
Document type	Journal Article
ZDB-ID	1193674-5
ISSN	1532-2653 ; 0967-5868
ISSN (online)	1532-2653
ISSN	0967-5868
DOI	10.1016/j.jocn.2021.07.010
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Zs.A 3999: Show issues

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bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article: Microstructure of embolized capsule of chronic subdural hematoma.

Stanishevskiy, Artem / Jakovenko, Andrew / Ryzhova, Marina / Svistov, Dmitry / Gizatullin, Shamil Kh / Babichev, Konstantin / Vinogradov, Evgeniy / Chemodakova, Ksenia

Surgical neurology international

2022 Volume 13, Page(s) 531

Abstract: Background: Chronic subdural hematomas (cSDHs) are frequent and potentially life-threatening neurosurgical conditions affecting, first of all, elderly. Few treatment options are available ranging from observation to removal thought large craniotomy. ... ...

Abstract	Background: Chronic subdural hematomas (cSDHs) are frequent and potentially life-threatening neurosurgical conditions affecting, first of all, elderly. Few treatment options are available ranging from observation to removal thought large craniotomy. However, currently, there is tendency to minimize surgical aggression, especially considering poor general condition of elderly patients. Thus, one of gaining popularity method of neurointerventional treatment of cSDHs is medial meningeal artery (MMA) embolization. To date, large series of cases published describing favorable outcomes of this treatment approach. At the same time, few reports are available that describe microstructural changes in cSDH's capsule after embolization; meanwhile, no exact effect of embolization on pathophysiology of hematoma was determined. Case description: Through current paper, we present two cases of cSDH that has previously undergone embolization of MMA, after which cSDHs have been operated through minicraniotomy due to complications after artery embolization. Microstructural changes of hematoma's capsule are described and discussed. Conclusion: Histological changes in embolized capsule suggest embolization of MMA as a valuable method for treatment of cSDHs.
Language	English
Publishing date	2022-11-18
Publishing country	United States
Document type	Case Reports
ISSN	2229-5097
ISSN	2229-5097
DOI	10.25259/SNI_691_2022
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Article ; Online: Second-hit APC mutation in a familial adamantinomatous craniopharyngioma.

Gorelyshev, Alexander / Mazerkina, Nadia / Medvedeva, Olga / Vasilyev, Evgeny / Petrov, Vasily / Ryzhova, Marina / Gorelyshev, Sergey / Tiulpakov, Anatoly

Neuro-oncology

2020 Volume 22, Issue 6, Page(s) 889–891

MeSH term(s)	Adenomatous Polyposis Coli Protein/genetics ; Adult ; Craniopharyngioma/genetics ; Female ; Humans ; Mutation ; Pituitary Neoplasms/genetics ; Young Adult ; beta Catenin/genetics
Chemical Substances	APC protein, human ; Adenomatous Polyposis Coli Protein ; beta Catenin
Language	English
Publishing date	2020-03-13
Publishing country	England
Document type	Case Reports ; Letter
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noaa060
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Zs.A 5307: Show issues

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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)

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Article: Spontaneous Transformation of Vestibular Schwannoma into Malignant Peripheral Nerve Sheath Tumor.

Belyaev, Artem / Usachev, Dmitry / Shimansky, Vadim / Odamanov, Dzhemil / Shishkina, Lyudmila / Ryzhova, Marina / Golanov, Andrey

Asian journal of neurosurgery

2018 Volume 13, Issue 3, Page(s) 810–813

Abstract: Although radiosurgery-induced transformation of vestibular schwannoma (VS) into malignant peripheral nerve sheath tumor (MPNST) is being widely discussed, little attention is paid to the spontaneous transition of these tumors. Although the pathogenesis ... ...

Abstract	Although radiosurgery-induced transformation of vestibular schwannoma (VS) into malignant peripheral nerve sheath tumor (MPNST) is being widely discussed, little attention is paid to the spontaneous transition of these tumors. Although the pathogenesis of this phenomenon remains uncertain, growing number of reported cases might call to notice them. We present a case of a 29-year-old woman who suffered right-sided hearing loss which remained untreated for 4.5 years. Magnetic resonance imaging revealed a right cerebellopontine tumor and the patient underwent tumor removal through retrosigmoid approach. Pathologically, the tumor was benign acoustic schwannoma with increased Ki-67 8%-10%. The tumor relapsed only 6 months later and was removed again-this time it was malignant peripheral nerve sheath tumor MPNST. The patient was treated with stereotactic radiotherapy, but despite that tumor growth was observed again and she underwent the third operation. Later on, tumor progression was noted with multiple intraaxial metastases and patient died 17 months after the diagnosis of MPNST had been confirmed. This is a seventh documented case of spontaneous transformation of VS into MPNST, which is clinically important for recording.
Language	English
Publishing date	2018-09-28
Publishing country	India
Document type	Case Reports
ZDB-ID	2621446-5
ISSN	2248-9614 ; 1793-5482
ISSN (online)	2248-9614
ISSN	1793-5482
DOI	10.4103/ajns.AJNS_251_16
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Article ; Online: Study of Simple Immunohistochemical Cytocolorimetric Assay Application for More Accurate Assessment of Prognosis in Patients with Pituitary Adenomas.

Nikitin, Pavel V / Ryzhova, Marina V / Shishkina, Lyudmila V / Shugay, Svetlana V / Zubova, Irina V

World neurosurgery

2018 Volume 122, Page(s) e1047–e1051

Abstract: Background: Immunohistochemistry is a basic diagnostic technique. Immunohistochemical examination results reflect mainly qualitative and less quantitative characteristics of proteomic status of cells. A combined approach with complex quantitative ... ...

Abstract	Background: Immunohistochemistry is a basic diagnostic technique. Immunohistochemical examination results reflect mainly qualitative and less quantitative characteristics of proteomic status of cells. A combined approach with complex quantitative evaluation of marker expression using colorimetric analysis and computer technologies can expand the diagnostic capabilities of immunohistochemistry. We studied such an approach developed by using expression of the proliferative marker Ki-67 in pituitary adenomas. Methods: A retrospective, blind, randomized, comparative study was performed of Ki-67 expression activity in pituitary adenomas using the traditional Ki-67 labeling index and a simple immunohistochemical cytocolorimetric analysis developed by us with immunohistochemical cytocolorimetric index (ICI) estimation as predictors of relapse, assessing the relationships of these indicators with the time before relapse. Results: Mean Ki-67 labeling index was 3.87% ± 0.29% in the relapse-free group and 4.01% ± 0.29% in the relapse group; the difference was not statistically significant. The average Ki-67 ICI was 24.16% ± 0.51% in the relapse-free group and 30.68% ± 0.64% in the relapse group; the difference was statistically significant. The correlation coefficient of ICI values and time before relapse was -0.302, indicating the presence of a weak negative correlation. Conclusions: We successfully tested an ICI estimation method developed by us to assess Ki-67 expression in pituitary adenomas. The ICI technique can be used both as a prognostic factor for relapse and, in combination with other modern proteomic and genetic methods, as the basis for creation of new multimodal analyzing systems for functional state assessment of cells and tissues.
MeSH term(s)	Adenoma/diagnosis ; Adenoma/metabolism ; Adult ; Biomarkers, Tumor/biosynthesis ; Colorimetry/standards ; Female ; Humans ; Ki-67 Antigen/analysis ; Ki-67 Antigen/biosynthesis ; Male ; Middle Aged ; Pituitary Neoplasms/diagnosis ; Pituitary Neoplasms/metabolism ; Prognosis ; Retrospective Studies ; Single-Blind Method
Chemical Substances	Biomarkers, Tumor ; Ki-67 Antigen
Language	English
Publishing date	2018-11-09
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2018.10.225
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Zs.A 1159: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
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ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Integrated molecular analysis of adult sonic hedgehog (SHH)-activated medulloblastomas reveals two clinically relevant tumor subsets with VEGFA as potent prognostic indicator.

Korshunov, Andrey / Okonechnikov, Konstantin / Stichel, Damian / Ryzhova, Marina / Schrimpf, Daniel / Sahm, Felix / Sievers, Philipp / Absalyamova, Oksana / Zheludkova, Olga / Golanov, Andrey / Jones, David T W / Pfister, Stefan M / von Deimling, Andreas / Kool, Marcel

Neuro-oncology

2021 Volume 23, Issue 9, Page(s) 1576–1585

Abstract: Background: Up to now, adult medulloblastoma (MB) patients are treated according to the protocols elaborated for pediatric MB although these tumors are different in terms of clinical outcomes and biology. Approximately 70% of adult MB disclose a sonic ... ...

Abstract	Background: Up to now, adult medulloblastoma (MB) patients are treated according to the protocols elaborated for pediatric MB although these tumors are different in terms of clinical outcomes and biology. Approximately 70% of adult MB disclose a sonic hedgehog (SHH) molecular signature in contrast to about 30% in pediatric cohorts. In addition, adult SHH-MB (aSHH-MB) are clinically heterogeneous but there is consensus neither on their optimal treatment nor on risk stratification. Thus, the identification of clinically relevant molecular subsets of aSHH-MB and identification of potential treatment targets remains inconclusive. Methods: We analyzed 96 samples of institutionally diagnosed aSHH-MB through genome-wide DNA methylation profiling, targeted DNA sequencing, and RNA sequencing to identify molecular subcategories of these tumors and assess their prognostic significance. Results: We defined two aSHH-MB numerically comparable epigenetic subsets with clinical and molecular variability. The subset "aSHH-MBI" (46%/48%) was associated with PTCH1/SMO (54%/46%) mutations, "neuronal" transcriptional signatures, and favorable outcomes after combined radio-chemotherapy (5-year PFS = 80% and OS = 92%). The clinically unfavorable "aSHH-MBII" subset (50%/52%; 5-year PFS = 24% and OS = 45%) disclosed GLI2 amplifications (8%), loss of 10q (22%), and gene expression signatures associated with angiogenesis and embryonal development. aSHH-MBII tumors revealed strong and ubiquitous expression of VEGFA both at transcript and protein levels that was correlated with unfavorable outcome. Conclusions: (1) The histologically uniform aSHH-MB cohort exhibits clear molecular heterogeneity separating these tumors into two molecular subsets (aSHH-MBI and aSHH-MBII), which are associated with different cytogenetics, mutational landscapes, gene expression signatures, and clinical course. (2) VEGFA appears to be a promising biomarker to predict clinical course, which needs further prospective validation as its potential role in the pathogenesis of this subset.
MeSH term(s)	Adult ; Cerebellar Neoplasms/genetics ; Child ; Hedgehog Proteins/genetics ; Humans ; Medulloblastoma/genetics ; Prognosis ; Transcriptome ; Vascular Endothelial Growth Factor A
Chemical Substances	Hedgehog Proteins ; SHH protein, human ; VEGFA protein, human ; Vascular Endothelial Growth Factor A
Language	English
Publishing date	2021-02-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2028601-6
ISSN	1523-5866 ; 1522-8517
ISSN (online)	1523-5866
ISSN	1522-8517
DOI	10.1093/neuonc/noab031
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Zs.A 5307: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: ABCB1 inhibition provides a novel therapeutic target to block TWIST1-induced migration in medulloblastoma.

Nasir, Aishah / Cardall, Alice / Othman, Ramadhan T / Nicolaou, Niovi / Lourdusamy, Anbarasu / Linke, Franziska / Onion, David / Ryzhova, Marina / Cameron, Hanna / Valente, Cara / Ritchie, Alison / Korshunov, Andrey / Pfister, Stefan M / Grabowska, Anna M / Kerr, Ian D / Coyle, Beth

Neuro-oncology advances

2021 Volume 3, Issue 1, Page(s) vdab030

Abstract: Background: Therapeutic intervention in metastatic medulloblastoma is dependent on elucidating the underlying metastatic mechanism. We investigated whether an epithelial-mesenchymal transition (EMT)-like pathway could drive medulloblastoma metastasis.!## ...

Abstract	Background: Therapeutic intervention in metastatic medulloblastoma is dependent on elucidating the underlying metastatic mechanism. We investigated whether an epithelial-mesenchymal transition (EMT)-like pathway could drive medulloblastoma metastasis. Methods: A 3D Basement Membrane Extract (3D-BME) model was used to investigate medulloblastoma cell migration. Cell line growth was quantified with AlamarBlue metabolic assays and the morphology assessed by time-lapse imaging. Gene expression was analyzed by qRT-PCR and protein expression by immunohistochemistry of patient tissue microarrays and mouse orthotopic xenografts. Chromatin immunoprecipitation was used to determine whether the EMT transcription factor TWIST1 bound to the promoter of the multidrug pump Results: Metastatic cells migrated to form large metabolically active aggregates, whereas non-tumorigenic/non-metastatic cells formed small aggregates with decreasing metabolic activity. TWIST1 expression was upregulated in the 3D-BME model. TWIST1 and ABCB1 were significantly associated with metastasis in patients ( Conclusions: In this study, we identified a TWIST1-ABCB1 signaling axis during medulloblastoma migration, which can be therapeutically targeted with the clinically approved ABCB1 inhibitor, vardenafil.
Language	English
Publishing date	2021-04-28
Publishing country	England
Document type	Journal Article
ZDB-ID	3009682-0
ISSN	2632-2498 ; 2632-2498
ISSN (online)	2632-2498
ISSN	2632-2498
DOI	10.1093/noajnl/vdab030
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