Enhanced antitumor effect of YM872 and AG1296 combination treatment on human glioblastoma xenograft models

Watanabe, Takashi; Ohtani, Toshiyuki; Aihara, Masanori; Ishiuchi, Shogo

doi:10.3171/2012.11.jns12362

Cited by 6 publications

(5 citation statements)

References 37 publications

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“…The present study examined the effect of tyrphostin AG 1296 on glioblastoma cell growth and migration in vitro and in vivo . In accordance with previous studies ( 23 , 24 ), tyrphostin AG 1296 exhibited marked efficacy in the inhibition of glioblastoma cell growth and migration in vitro . Furthermore, it was demonstrated that tyrphostin AG 1296 induced cell apoptosis in vitro and in vivo .…”

Section: Discussionsupporting

confidence: 92%

“…Previous studies have suggested that tyrphostin AG 1296, an inhibitor of PDGFR, reduces glioblastoma cell proliferation ( 24 ). In order to confirm whether tyrphostin AG 1296 affects glioblastoma cell growth, a cell viability assay was performed in U87MG cells.…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that tyrphostin AG 1296 inhibits cell proliferation and promotes apoptosis in small cell lung cancer, leukemia and anaplastic thyroid cancer ( 20 – 22 ). Recently, it has been suggested that AG 1296 may suppress the proliferation and migration of glioblastoma cells ( 23 , 24 ). Whilst tyrphostin AG 1296 has been shown to affect the proliferation and migration of glioblastoma cells, its effect on the rate of apoptosis in GBM remains unclear.…”

Section: Introductionmentioning

confidence: 99%

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Tyrphostin AG 1296 induces glioblastoma cell apoptosis in vitro and in vivo

Zheng²,

Guan³

et al. 2015

Oncology Letters

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Glioblastoma is the most common type of malignant human brain tumor. Currently available chemotherapies for glioblastoma focus on targeting tyrosine kinases. However, the existing inhibitors of tyrosine kinases have not produced the therapeutic outcomes that were anticipated. In order to investigate the viability alternative chemotherapeutic agents in this disease, the present study examined the anticancer effects of tyrphostin AG 1296, focusing on its involvement in apoptosis in glioblastoma cells. The study aimed to identify whether tyrphostin AG 1296 affects glioblastoma cell growth by inducing cell apoptosis. To achieve this, cell viability, propidium iodide analysis and cell invasion assay were used to measure cell growth, cell apoptosis and cell migration of human glioblastoma cells. The results showed that tyrphostin AG 1296 treatment reduced cell viability and suppressed migration of human glioblastoma cells. It was also demonstrated that tyrphostin AG 1296 induced cell apoptosis in vitro. Finally, tyrphostin AG 1296 was also shown to significantly inhibit the growth of glioblastoma cells and to increase tumor cell apoptosis in vivo. These findings suggest that tyrphostin AG 1296 induces apoptosis, thereby reducing cell viability and capacity for migration of glioblastoma cells.

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Section: Discussionsupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tyrphostin AG 1296 induces glioblastoma cell apoptosis in vitro and in vivo

Zheng²,

Guan³

et al. 2015

Oncology Letters

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“…Targeting ionotropic glutamate receptors to reduce proliferation and invasion of GB, promising preclinical data exist inter-alia for AMPAR- and NMDAR-inhibitors including memantine [ 3 , 6 , 8 , 11 , 15 , 16 , 20 , 46 ]. As radiotherapy plays a central role in GB treatment, testing for radiosensitizing potential of glutamate receptor targeted therapy to enhance irradiation’s effectiveness appears sensible especially from a clinical perspective.…”

Section: Discussionmentioning

confidence: 99%

Combining a noble gas with radiotherapy: glutamate receptor antagonist xenon may act as a radiosensitizer in glioblastoma

Büttner,

Maerevoet,

Giordano

et al. 2024

Radiat Oncol

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Background Ionotropic glutamate receptors α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) and N-methyl-D-aspartate receptor (NMDAR) modulate proliferation, invasion and radioresistance in glioblastoma (GB). Pharmacological targeting is difficult as many in vitro-effective agents are not suitable for in patient applications. We aimed to develop a method to test the well tolerated AMPAR- and NMDAR-antagonist xenon gas as a radiosensitizer in GB. Methods We designed a diffusion-based system to perform the colony formation assay (CFA), the radiobiological gold standard, under xenon exposure. Stable and reproducible gas atmosphere was validated with oxygen and carbon dioxide as tracer gases. After checking for AMPAR and NMDAR expression via immunofluorescence staining we performed the CFA with the glioblastoma cell lines U87 and U251 as well as the non-glioblastoma derived cell line HeLa. Xenon was applied after irradiation and additionally tested in combination with NMDAR antagonist memantine. Results The gas exposure system proved compatible with the CFA and resulted in a stable atmosphere of 50% xenon. Indications for the presence of glutamate receptor subunits were present in glioblastoma-derived and HeLa cells. Significantly reduced clonogenic survival by xenon was shown in U87 and U251 at irradiation doses of 4–8 Gy and 2, 6 and 8 Gy, respectively (p < 0.05). Clonogenic survival was further reduced by the addition of memantine, showing a significant effect at 2–8 Gy for both glioblastoma cell lines (p < 0.05). Xenon did not significantly reduce the surviving fraction of HeLa cells until a radiation dose of 8 Gy. Conclusion The developed system allows for testing of gaseous agents with CFA. As a proof of concept, we have, for the first time, unveiled indications of radiosensitizing properties of xenon gas in glioblastoma.

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“…In Fibroblasten und kolorektalen Karzinomzelllinien konnte außerdem gezeigt werden, dass SRC einen Komplex mit EGFR bilden kann, in dessen Folge der EGFR und die nachfolgenden Signalwege auch ohne Ligandenbindung aktiviert werden (Maa et al, 1995, Stover et al, 1995. einen Arrest der Zellen in der G1-Phase des Zellzyklus bewirkt (Vigneron et al, 2005, Mamidipudi et al, 2007, Hikita et al, 2010 Ergebnisse der PDGFR-β-Inhibition in Prostatakarzinom-, Glioblastom-, Bronchialkarzinomund Kolonkarzinomzellen zeigen jedoch (Roberts et al, 2005, Yokoi et al, 2005, Park et al, 2011, Watanabe et al, 2013…”

Section: Mittels Immunzytochemischemunclassified

Die Rolle der IGF-Achse in Kombination mit anderen Wachstumsfaktor-Signalwegen bei der Resistenz oder dem Ansprechen von kolorektalen Karzinomen auf eine Radiochemotherapie

Seemann¹

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Enhanced antitumor effect of YM872 and AG1296 combination treatment on human glioblastoma xenograft models

Abstract: The strongly enhanced antitumor effect of this combination therapy in vivo rather than in vitro may be attributable to disruption of the aberrant vascular niche. This combination therapy might provide substantial benefits to patients with glioblastoma.

Cited by 6 publications

References 37 publications

Tyrphostin AG 1296 induces glioblastoma cell apoptosis in vitro and in vivo

Tyrphostin AG 1296 induces glioblastoma cell apoptosis in vitro and in vivo

Combining a noble gas with radiotherapy: glutamate receptor antagonist xenon may act as a radiosensitizer in glioblastoma

Die Rolle der IGF-Achse in Kombination mit anderen Wachstumsfaktor-Signalwegen bei der Resistenz oder dem Ansprechen von kolorektalen Karzinomen auf eine Radiochemotherapie

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