The algorithms of adjuvant therapy in gliomas and their effect on survival

Straube, Christoph; Schmidt‐Graf, Friederike; Wiestler, Benedikt; Zimmer, Claus; Meyer, Bernhard; Combs, Stephanie E.

doi:10.23736/s0390-5616.18.04610-6

Cited by 5 publications

(2 citation statements)

References 42 publications

(63 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…According to the 2016 World Health Organization (WHO) classification of CNS tumors, diffuse gliomas are classified based on histological (astrocytoma, oligoastrocytoma, oligodendroglioma and glioblastoma) and genetic features [isocitrate dehydrogenase mutations, alpha-thalassemia/mental retardation, X-linked (ATRX) loss, TP53 mutation and 1p/19q-codeletion] ( 2 ). In addition, the WHO classified CNS tumors into 4 grades (I–IV) that have distinct prognosis and require different therapeutic decisions ( 3 , 4 ). Glioblastomas (grade IV), which correspond to ~50% of gliomas are highly malignant gliomas with a poor prognosis ( 5 , 6 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting glioma cells by antineoplastic activity of reversine

et al. 2021

View full text Add to dashboard Cite

Gliomas are the most common type of primary central nervous system tumors and despite great advances in understanding the molecular basis of the disease very few new therapies have been developed. Reversine, a synthetic purine analog, is a multikinase inhibitor that targets aurora kinase A (AURKA) and aurora kinase B (AURKB). In gliomas, a high expression of AURKA or AURKB is associated with a malignant phenotype and a poor prognosis. The present study investigated reversine-related cellular and molecular antiglioma effects in HOG, T98G and U251MG cell lines. Gene and protein expression were assessed by reverse transcription-quantitative PCR and western blotting, respectively. For functional assays, human glioma cell lines (HOG, T98G and U251MG) were exposed to increasing concentrations of reversine (0.4–50 µM) and subjected to various cellular and molecular assays. Reversine reduced the viability and clonogenicity in a dose- and/or time-dependent manner in all glioma cells, with HOG (high AURKB-expression) and T98G (high AURKA-expression) cells being more sensitive compared with U251MG cells (low AURKA- and AURKB-expression). Notably, HOG cells presented higher levels of polyploidy, while T98G presented multiple mitotic spindles, which is consistent with the main regulatory functions of AURKB and AURKA, respectively. In molecular assays, reversine reduced AURKA and/or AURKB expression/activity and increased DNA damage and apoptosis markers, but autophagy-related proteins were not modulated. In conclusion, reversine potently induced mitotic catastrophe and apoptosis in glioma cells and higher basal levels of aurora kinases and genes responsive to DNA damage and may predict improved antiglioma responses to the drug. Reversine may be a potential novel drug in the antineoplastic arsenal against gliomas.

show abstract

Section: Introductionmentioning

confidence: 99%

Targeting glioma cells by antineoplastic activity of reversine

et al. 2021

View full text Add to dashboard Cite

show abstract

“…In particular, in case of CNS, at least half of these patients receive whole brain radiotherapy (WBRT), therefore RT long-term side effects on cognitive performance represents a major concern that can significantly impact in terms of QoL on both patients and caregivers. Although in these patients RT occupies a pivotal role, due to the interaction of ionizing radiations on brain cells, it also has side effects that could appear as early as 3-4 months later with cognitive decline being the most common and affecting patients with memory loss and/or impairments in executive functions, particularly in case of WBRT [62].…”

Section: Discussionmentioning

confidence: 99%

The Molecular Effects of Ionizing Radiations on Brain Cells: Radiation Necrosis vs. Tumor Recurrence

et al. 2019

View full text Add to dashboard Cite

The central nervous system (CNS) is generally resistant to the effects of radiation, but higher doses, such as those related to radiation therapy, can cause both acute and long-term brain damage. The most important results is a decline in cognitive function that follows, in most cases, cerebral radionecrosis. The essence of radio-induced brain damage is multifactorial, being linked to total administered dose, dose per fraction, tumor volume, duration of irradiation and dependent on complex interactions between multiple brain cell types. Cognitive impairment has been described following brain radiotherapy, but the mechanisms leading to this adverse event remain mostly unknown. In the event of a brain tumor, on follow-up radiological imaging often cannot clearly distinguish between recurrence and necrosis, while, especially in patients that underwent radiation therapy (RT) post-surgery, positron emission tomography (PET) functional imaging, is able to differentiate tumors from reactive phenomena. More recently, efforts have been done to combine both morphological and functional data in a single exam and acquisition thanks to the co-registration of PET/MRI. The future of PET imaging to differentiate between radionecrosis and tumor recurrence could be represented by a third-generation PET tracer already used to reveal the spatial extent of brain inflammation. The aim of the following review is to analyze the effect of ionizing radiations on CNS with specific regard to effect of radiotherapy, focusing the attention on the mechanism underling the radionecrosis and the brain damage, and show the role of nuclear medicine techniques to distinguish necrosis from recurrence and to early detect of cognitive decline after treatment.

show abstract