Effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors

Donnelly, Erling T.; Liu, Yanfeng; Fatunmbi, Yetunde O; Lee, Intae; Magda, Darren; Rockwell, Sara

doi:10.1016/j.ijrobp.2003.12.017

Cited by 24 publications

(15 citation statements)

References 35 publications

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“…MGd has also been shown to increase the oxygen tension in tumors. In a recent study, the oxygenation of EMT6 mammary tumor in mice was measured with and without the injection of MGd [44]. Increased median pO 2 levels in tumors were significantly increased by MGd compared to controls.…”

Section: Discussionmentioning

confidence: 99%

Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

et al. 2008

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Photodynamic therapy (PDT) has been investigated as a postoperative treatment in patients with high grade gliomas. The purpose of this in vitro investigation was to determine whether motexafin gadolinium (MGd), a known radiation sensitizer, could potentiate the effects of 5-aminolevulinic acid (ALA)-PDT. Human glioma (ACBT) spheroids (250 μm diameter) were incubated in 5-aminolevulinic acid (ALA) with and without MGd and irradiated with 635 nm light for a total light fluence of 6, 12, or 18 J cm−2 delivered at a fluence rate of 5 mW cm−2. Spheroid growth was monitored for a period of 4 weeks following each treatment. In another set of experiments, 400–500 μm diameter ACBT spheroids were implanted into a gel collagen matrix and subjected to ALA-PDT (fluence: 3 or 6 J cm−2), MGd, or a combination of ALA-PDT and MGd. The migration distance of surviving glioma cells in each treatment group was recorded over a 5-day period. The results showed that MGd interacted with PDT in a synergistic manner resulting in greater cytotoxicity than that achievable with either treatment modality alone. The degree of synergism was shown to increase with increasing light fluence. At the highest light fluence investigated (18 J cm−2), the percentage of spheroids demonstrating growth 4 weeks following exposure to MGd, ALA-PDT, or MGd + ALA-PDT was 100%, 75%, and 15%, respectively. The results of cell migration studies revealed that the combination of PDT and MGd produced a significant inhibitory effect on glioma cell migration: the addition of MGd resulted in an approximately three times reduction in migration distance compared with PDT alone. Overall, the results suggest that MGd can potentiate both the cytotoxic and migration inhibitory effects of ALA-PDT and hence, this combined therapeutic approach has the potential to extend treatment volumes in patients with malignant gliomas.

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Section: Discussionmentioning

confidence: 99%

Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

et al. 2008

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“…MGd is easily reduced (half-wave potential 50 mV versus normal hydrogen electrode), and in vitro, it may catalyze slow oxidation of intracellular reducing metabolites such as ascorbate, GSH, and NADPH, generating superoxide and reactive oxygen species (ROS) in a process called futile redox cycling (6). The drug is known to enhance treatment of tumor cells by radiation and cytotoxic drugs (7)(8)(9). Generation of ROS in myeloma cells and induction of apoptosis has been demonstrated (10).…”

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confidence: 99%

Motexafin Gadolinium, a Tumor-selective Drug Targeting Thioredoxin Reductase and Ribonucleotide Reductase

Hashemy¹,

Ungerstedt²,

Avval

et al. 2006

Journal of Biological Chemistry

149

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“…Thioredoxin reductase generates reactive oxygen species, thus creating intracellular oxidative stress [32]. A further intriguing observation suggests that motexafin gadolinium actually increases intracellular oxygen levels, thereby potentially overcoming hypoxia and allowing 'fixation' of radiation damage [33]. Motexafin gadolinium may selectively induce damage in these cells.…”

Section: Pharmacodynamics and Mechanism Of Actionmentioning

confidence: 99%

Motexafin gadolinium: a novel radiosensitizer for brain tumors

Forouzannia

Richards

Khuntia

et al. 2007

Expert Review of Anticancer Therapy

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Despite advances in the field of oncology, progress for patients with brain metastases and most primary brain tumors has been slow. New efforts to enhance the therapeutic index of radiation therapy are under way, including the use of radiosensitizers. Motexafin gadolinium (Xcytrin) is one such novel agent with several unique properties that enhance the cytotoxic potential of radiation therapy, as well as several chemotherapeutic agents, and possibly has independent cytotoxicity in certain lymphoid malignancies. Motexafin gadolinium is very well tolerated with tumor specific uptake. The rationale for the use of this drug as well as its current and future role as a radiation enhancer in the management of brain tumors is reviewed.

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Effects of texaphyrins on the oxygenation of EMT6 mouse mammary tumors

Cited by 24 publications

References 35 publications

Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

Motexafin gadolinium enhances the efficacy of aminolevulinic acid mediated-photodynamic therapy in human glioma spheroids

Motexafin Gadolinium, a Tumor-selective Drug Targeting Thioredoxin Reductase and Ribonucleotide Reductase

Motexafin gadolinium: a novel radiosensitizer for brain tumors

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