Synergistic effect of arsenic trioxide, vismodegib and temozolomide on glioblastoma

Bureta, Costansia; Saitoh, Yoshinobu; Tokumoto, Hiroto; Sasaki, Hiromi; Maeda, Shingo; Nagano, Satoshi; Komiya, Setsuro; Taniguchi, Noboru; Setoguchi, Takao

doi:10.3892/or.2019.7100

Cited by 20 publications

(18 citation statements)

References 45 publications

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“…compared the effects of temozolomide combined either with arsenic trioxide or with the Hedgehog pathway inhibitor vismodegib. Both combinations increased the anti-glioma effect of temozolomide, with similar effects, and inhibited the Hedgehog pathway in glioblastoma [ 56 ].…”

Section: Inhibitory Effects Of Arsenic Trioxide On Glioma Stem Cellsmentioning

confidence: 99%

Arsenic trioxide as a novel anti-glioma drug: a review

Fang

Zhang

2020

Cell Mol Biol Lett

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Arsenic trioxide has shown a strong anti-tumor effect with little toxicity when used in the treatment of acute promyelocytic leukemia (APL). An effect on glioma has also been shown. Its mechanisms include regulation of apoptosis and autophagy; promotion of the intracellular production of reactive oxygen species, causing oxidative damage; and inhibition of tumor stem cells. However, glioma cells and tissues from other sources show different responses to arsenic trioxide. Researchers are working to enhance its efficacy in anti-glioma treatments and reducing any adverse reactions. Here, we review recent research on the efficacy and mechanisms of action of arsenic trioxide in the treatment of gliomas to provide guidance for future studies.

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Section: Inhibitory Effects Of Arsenic Trioxide On Glioma Stem Cellsmentioning

confidence: 99%

Arsenic trioxide as a novel anti-glioma drug: a review

Fang

Zhang

2020

Cell Mol Biol Lett

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“…Glioblastoma is defined as a grade IV tumor characterized by high heterogeneity and a dismal prognosis, according to the World Health Organization guidelines . The current first‐line treatment for newly diagnosed GBM is maximal safe resection followed by chemoradiation . Despite aggressive interventions, the disease almost inevitably turns into recurrent GBM, for which no standard and effective treatment approach has been shown to prolong patient survival significantly .…”

Section: Introductionmentioning

confidence: 99%

Role of alternative splicing signatures in the prognosis of glioblastoma

Xie

Dang

et al. 2019

Cancer Medicine

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Background Increasing evidence has validated the crucial role of alternative splicing (AS) in tumors. However, comprehensive investigations on the entirety of AS and their clinical value in glioblastoma (GBM) are lacking. Methods The AS profiles and clinical survival data related to GBM were obtained from The Cancer Genome Atlas database. Univariate and multivariate Cox regression analyses were performed to identify survival‐associated AS events. A risk score was calculated, and prognostic signatures were constructed using seven different types of independent prognostic AS events, respectively. The Kaplan‐Meier estimator was used to display the survival of GBM patients. The receiver operating characteristic curve was applied to compare the predictive efficacy of each prognostic signature. Enrichment analysis and protein interactive networks were conducted using the gene symbols of the AS events to investigate important processes in GBM. A splicing network between splicing factors and AS events was constructed to display the potential regulatory mechanism in GBM. Results A total of 2355 survival‐associated AS events were identified. The splicing prognostic model revealed that patients in the high‐risk group have worse survival rates than those in the low‐risk group. The predictive efficacy of each prognostic model showed satisfactory performance; among these, the Alternate Terminator (AT) model showed the best performance at an area under the curve (AUC) of 0.906. Enrichment analysis uncovered that autophagy was the most enriched process of prognostic AS gene symbols in GBM. The protein network revealed that UBC, VHL, KCTD7, FBXL19, RNF7, and UBE2N were the core genes in GBM. The splicing network showed complex regulatory correlations, among which ELAVL2 and SYNE1_AT_78181 were the most correlated (r = −.506). Conclusions Applying the prognostic signatures constructed by independent AS events shows promise for predicting the survival of GBM patients. A splicing regulatory network might be the potential splicing mechanism in GBM.

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“…28 To combat this unacceptable toxicity, one strategy, which is not unique to arsenical therapies, is to combine 2 drugs hoped to act in synergy at lower doses to achieve the same benefit with less toxicity. [29][30][31][32] One example of this adjuvant/combination strategy is the pairing of arsenic trioxide and carnosic acid. The combination of the 2 drugs, and each drug separately, has been tested on long-telomere mice, derived from BALB mice bred in captivity since at least 1913.…”

Section: Acute Toxicity Of Arsenicalsmentioning

confidence: 99%

Telomere Length and Arsenic: Improving Animal Models of Toxicity by Choosing Mice With Shorter Telomeres

Whitlock

2021

Int J Toxicol

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Arsenic is both a chemotherapeutic drug and an environmental toxicant that affects hundreds of millions of people each year. Arsenic exposure in drinking water has been called the worst poisoning in human history. How arsenic is handled in the body is frequently studied using rodent models to investigate how arsenic both causes and treats disease. These models, used in a variety of arsenic-related testing, from tumor formation to drug toxicity monitoring, have virtually always been developed from animals with telomeres that are unnaturally long, likely because of accidental artificial selective pressures. Mice that have been bred in captivity in laboratory conditions, often for over 100 years, are the standard in creating animal models for this research. Using these mice introduces challenges to any work that can be affected by the length of telomeres and the related capacities for tissue repair and cancer resistance. However, arsenic research is particularly susceptible to the misuse of such animal models due to the multiple and various interactions between arsenic and telomeres. Researchers in the field commonly find mouse models and humans behaving very differently upon exposure to acute and chronic arsenic, including drug therapies which seem safe in mice but are toxic in humans. Here, some complexities and apparent contradictions of the arsenic carcinogenicity and toxicity research are reconciled by an explanatory model that involves telomere length explained by the evolutionary pressures in laboratory mice. A low-risk hypothesis is proposed which has the power to determine whether researchers can easily develop more powerful and accurate mouse models by simply avoiding mouse lineages that are very old and have strangely long telomeres. Swapping in newer mouse lineages for the older, long-telomere mice may vastly improve our ability to research arsenic toxicity with virtually no increase in cost or difficulty of research.

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Synergistic effect of arsenic trioxide, vismodegib and temozolomide on glioblastoma

Cited by 20 publications

References 45 publications

Arsenic trioxide as a novel anti-glioma drug: a review

Arsenic trioxide as a novel anti-glioma drug: a review

Role of alternative splicing signatures in the prognosis of glioblastoma

Telomere Length and Arsenic: Improving Animal Models of Toxicity by Choosing Mice With Shorter Telomeres

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