Glutamate Excitotoxicity and Its Role in Glioblastoma Biology
Ориентир для пациента и семьи
Простыми словами
Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.
- Что изучают
- В протоколе указаны: Blood, CSF and tumor samples.
- Кому может быть актуально
- Состояния в реестре: Brain Tumor, Primary. Базовые параметры: от 18 лет · Все.
- Что важно проверить
- Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
- Где проводится
- Италия
- Следующий шаг
- Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →
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Официальное название
Role of Glutamate-mediate Excitotoxicity in Invasion and Progression Processes of Glioblastoma Multiforme
Обзор
Gliomas are the most frequent type of primary brain tumors in adults; among them glioblastoma multiforme (GBM) is the most malignant, being associated with the worst prognosis. Glutamate (Glu) is an aminoacid, responsible for essential functions in the Central Nervous System (CNS), acting both as metabolite and neurotransmitter. It is essential for regulating cellular metabolism and developmental synaptogenesis, cellular migration, differentiation and death. Recent scientific evidences have demonstrated alteration in Glu synthesis and signaling being directly involved in GBM growth and invasion
Подробное описание
Glu and its scavenger's levels are measurable both in serum and in the cerebral-spinal fluid (CSF), thus making them ideal markers for tumor aggressiveness and disease activity as well as a potential target for new therapeutic approaches.
Serum and CSF levels of glutamic oxaloacetic transaminase (GOT1), Glutamate Pyruvate Transaminase (GPT) and glutamate and aspartate levels of a total of 40 patients will be collected.
Molecular biology analyses will be conducted and oncological and imaging data will be collected during follow-up in patients enrolled in the present studies. MRI imaging as well as blood sampling will be performed at definite timepoints (baseline and 3, 6 and 9 months follow-up).
Вмешательства
- Диагностический тест Blood, CSF and tumor samples
Blood, CSF and brain tissue sampling of Glu and Glu regulatory proteins.
Первичные конечные точки
- Baseline characterization of Glutamate scavengers (Glu-sca) levels in serum [Срок оценки: Baseline (before surgery)]
- Baseline characterization of Glutamate (Glu) levels in serum [Срок оценки: Baseline (before surgery)]
- Time changes in Glutamate scavengers (Glu-sca) levels in serum [Срок оценки: At 3, 6, 9 months following surgery]
- Time changes in Glutamate (Glu) levels in serum [Срок оценки: At 3, 6, 9 months following surgery]
Вторичные конечные точки (2)
- Characterization of Glutamate scavengers (Glu-sca) levels in cerebrospinal fluid (CSF) [Срок оценки: Baseline (before surgery)]
- Characterization of Glutamate (Glu) levels in cerebrospinal fluid (CSF) [Срок оценки: Baseline (before surgery)]
Критерии участия
Критерии включения
- Adult patients with a brain lesion suspected for GBM, candidate to gross total tumor resection (GTR), followed by radiotherapy and chemotherapy (concomitant and adjuvant).
- Patient able to provide informed consent.
Критерии исключения
- Age < 18 years
- Liver disease
- Severe anemia (Hb <8mg/dl)
- Pregnancy
Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.
Здоровые добровольцы: Нет
Дизайн исследования
- Модель наблюдения
- Когортное
Центры проведения
Италия · 1 центр
- IRCCS San Raffaele Scientific Institute — Milan
Публикации
- Olar A, Aldape KD. Using the molecular classification of glioblastoma to inform personalized treatment. J Pathol. 2014 Jan;232(2):165-77. doi: 10.1002/path.4282. PMID 24114756
- Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus PMID 15758009
- Wang W, Shi G, Ma B, Hao X, Dong X, Zhang B. Chemotherapy for Adults with Malignant Glioma: A Systematic Review and Network Meta-Analysis. Turk Neurosurg. 2017;27(2):174-181. doi: 10.5137/1019-5149.JTN.15462-15.0. PMID 27337236
- Robert SM, Sontheimer H. Glutamate transporters in the biology of malignant gliomas. Cell Mol Life Sci. 2014 May;71(10):1839-54. doi: 10.1007/s00018-013-1521-z. Epub 2013 Nov 27. PMID 24281762
- de Groot J, Sontheimer H. Glutamate and the biology of gliomas. Glia. 2011 Aug;59(8):1181-9. doi: 10.1002/glia.21113. Epub 2010 Dec 29. PMID 21192095
- O'Kane RL, Martinez-Lopez I, DeJoseph MR, Vina JR, Hawkins RA. Na(+)-dependent glutamate transporters (EAAT1, EAAT2, and EAAT3) of the blood-brain barrier. A mechanism for glutamate removal. J Biol Chem. 1999 Nov 5;274(45):31891-5. doi: 10.1074/jbc.274.45.31891. PMID 10542215
- Ruban A, Biton IE, Markovich A, Mirelman D. MRS of brain metabolite levels demonstrates the ability of scavenging of excess brain glutamate to protect against nerve agent induced seizures. Int J Mol Sci. 2015 Feb 2;16(2):3226-36. doi: 10.3390/ijms16023226. PMID 25648322
- Teichberg VI, Cohen-Kashi-Malina K, Cooper I, Zlotnik A. Homeostasis of glutamate in brain fluids: an accelerated brain-to-blood efflux of excess glutamate is produced by blood glutamate scavenging and offers protection from neuropathologies. Neuroscience. 2009 Jan 12;158(1):301-8. doi: 10.1016/j.neuroscience.2008.02.075. Epub 2008 Mar 18. PMID 18423998
Идентификаторы
NCT: NCT05775458 · NCH02-2020