Efficacy and Safety of Bevacizumab in Glioblastomas

Fazio, S. De; Russo, Emilio; Ammendola, Michele; Paola, Eugenio Donato Di; Sarro, Giovambattista De

doi:10.2174/092986712799320646

Cited by 21 publications

(9 citation statements)

References 68 publications

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“…Glioma is the most common and lethal primary intracranial tumour, with an incidence of 5/100,000 individuals 36 . Over the past decades, several agents, such as temozolomide (TMZ) and bevacizumab, have been used in clinical glioma therapy and have effectively improved the living quality of patients 3 , 37 . However, although great advances have been made in diagnosis and chemoradiotherapy, patient prognosis remains very poor.…”

Section: Discussionmentioning

confidence: 99%

Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis

Zhang

Pan

et al. 2018

Cell Death Dis

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Glioma is the most common and malignant form of primary brain tumour, and is characterised by high proliferation and extensive invasion and neurological destruction. Demethylzeylasteral (T-96), which is extracted from Tripterygium wilfordii, is considered to have immunosuppressive, anti-inflammatory and anti-angiogenic effects. Here, the anti-tumour effect of T-96 on glioma was evaluated. Our results demonstrated that T-96 significantly inhibited glioma cell growth and induced cell cycle arrest in G1 phase but did not induce apoptosis. Cell invasion and migration were dramatically suppressed after treatment with T-96. Almost all genes related to cell cycle and DNA replication were downregulated after treatment with T-96. Our results showed that miR-30e-5p was noticeably upregulated after T-96 treatment, and MYBL2, which is involved in cell cycle progression and is a target gene of miR-30e-5p, was significantly reduced in synchrony. Overexpression of MYBL2 partially rescued the T-96-induced inhibition of cell growth and proliferation. Moreover, a miR-30e-5p antagomir significantly reduced the upregulation of miR-30e-5p expression induced by T-96, leading to recovery of MYBL2 expression, and partially rescued the T-96-induced inhibition of cell growth and proliferation. More important, T-96 effectively upregulated miR-30e-5p expression and downregulated MYBL2 expression, thus inhibiting LN-229 cell tumour growth in a mouse model. These results indicated that T-96 might inhibit glioma cell growth by regulating the miR-30e-5p/MYBL2 axis. Our study demonstrated that T-96 might act as a promising agent for malignant glioma therapy.

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Section: Discussionmentioning

confidence: 99%

Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis

Zhang

Pan

et al. 2018

Cell Death Dis

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“…In the recurrent setting, after temozolomide failure, NEO212 may be used for these patients, as it is effective in temozolomide-resistant gliomas. Therefore, NEO212 would then provide a viable alternative to patients that would normally have gone to intravenous bevacizumab as their second line of therapy (49).…”

Section: Discussionmentioning

confidence: 99%

NEO212, Temozolomide Conjugated to Perillyl Alcohol, Is a Novel Drug for Effective Treatment of a Broad Range of Temozolomide-Resistant Gliomas

Cho¹,

Wang²,

Jhaveri³

et al. 2014

Molecular Cancer Therapeutics

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Patients with glioblastoma multiforme (GBM), a malignant primary brain tumor, inevitably develop resistance to standard-of-care chemotherapy, temozolomide. This study explores the effects of the novel agent NEO212, a conjugate of temozolomide to perillyl alcohol, on temozolomide-resistant gliomas. NEO212 was tested for cytotoxic activity on three human temozolomide-resistant glioma cell lines, which were resistant to temozolomide based on overexpression of the base excision repair (BER) pathway, mismatch repair (MMR) deficiency, or overexpression of O 6 methyl-guanine-DNA methyltransferase (MGMT). BER expression was evaluated by Western blotting and PARP activity. MMR deficiency was determined by Western blotting and microsatellite instability. MGMT overexpression was evaluated by Western blotting and O 6 -benzylguanine (O 6 BG) inhibition. For in vivo evaluation of NEO212, temozolomide-resistant glioma cells were implanted into immune-incompetent mice, and NEO212 was administered. NEO212, at equimolar concentrations of temozolomide, was more cytotoxic for temozolomideresistant cells than temozolomide and not toxic to normal cells. NEO212-induced cell death in temozolomide-resistant glioma cells was independent of such mechanisms of resistance as high levels of MGMT, MMR deficiencies, or overexpression of BER proteins. NEO212 functions as a DNA alkylating agent, similar to temozolomide; however, this novel conjugate is unique for it may induce endoplasmic reticulum (ER) stress and inhibits autophagy. In vivo studies show that NEO212 reduces intracranial tumor growth and increases animal survival without significant toxicity. These results demonstrate that NEO212 is an effective drug against malignant gliomas that can be used for a broad range of newly diagnosed and temozolomide-resistant gliomas.

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“…Glioma is a common malignant tumor originating from central glial cells and has devastating effects [1][2][3][4], LGG have long been considered to be a benign subgroup of clinical biological behaviors in brain gliomas,and there is growing evidence demonstrate that it is also a class II glioma[World Health Organization(WHO) 2016 classi cation], but its biological behavior and clinical prognosis are far different.Although there are many treatment options for glioma, their therapeutic e cacy is still unsatisfactory [5][6][7],the same therapy strategy,some patient with LGG after a tumor resection without recurrence but some one was found recurrence soon,so some patients have long-term OS or long-term FPS,some patients showed highly malignant outcome.Although in many previous studies,there are some factors like age,the extent resection, expression of some speci c genes et al that will affect the clinical outcome [8],however,so far,there is not exist a quantitative and accurate tool to evaluate the risk of recurrence after their rst surgery,so our group want develop a radiomics nomogram tool to predict the recurrent possibility. received their rst surgery between May 2017 and November 2019, the same dose and course of radiotherapy and chemotherapy were given after operation(Radiotherapy,total dose:50.4 Gy,1.8~2.0 Gy/28 times [9,10];chemotherapy:75mg/m 2 ,12/28 project,12 period.).…”

Section: Introductionmentioning

confidence: 99%

A Radiomics nomogram for preoperative predicting recurrence of low grade gliomas based on multiparametric MRI

Wang

Xiao

Zhang

et al. 2021

Preprint

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Objective To develop a radiomics nomogram to predict the recurrence of Low grade glioma(LGG) after their first surgery; Methods A retrospective analysis of pathological, clinical and Magnetic resonance image(MRI) of LGG patients who underwent surgery and had a recurrence between 2017 and 2020 in our hospital was performed. After a rigorous selection,64 patients were eligible and enrolled in the study(22 cases were with recurrent gliomas),which was randomly assigned in a 7:3 ratio to either the training set and validation set; T1WI,T2WI fluid-attenuated-inversion-recovery(T2WI-FLAIR) and contrast-enhanced T1-weighted(T1CE) sequences, 396 radiomics features were extracted from each image sequence, minimum-redundancy maximum-relevancy(mRMR) alone or combining with univariate logistic analysis were used for features screening, the screened features were performed by multivariate logistic regression analysis and developed a predictive model both in training set and validation set; Receiver operating characteristic(ROC) curve, calibration curve, and decision curve analysis(DCA) were used to assess the performance of each model. Results The radiomics nomogram derived from three MRI sequence yielded an ideal performance than the individual ones, the AUC in the training set and validation set were 0.966 and 0.93 respectively, 95% confidence interval(95%CI) were 0.949-0.99 and 0.905-0.973 respectively; the calibration curves indicated good agreement between the predictive and the actual probability. The DCA demonstrated that a combination of three sequences had more favorable clinical predictive value than single sequence imaging. Conclusion Our multiparametric radiomics nomogram could be an efficient and accurate tool for predicting the recurrence of LGG after its first resection.

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Efficacy and Safety of Bevacizumab in Glioblastomas

Cited by 21 publications

References 68 publications

Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis

Demethylzeylasteral inhibits glioma growth by regulating the miR-30e-5p/MYBL2 axis

NEO212, Temozolomide Conjugated to Perillyl Alcohol, Is a Novel Drug for Effective Treatment of a Broad Range of Temozolomide-Resistant Gliomas

A Radiomics nomogram for preoperative predicting recurrence of low grade gliomas based on multiparametric MRI

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