Radiation-Induced Astrogliosis and Blood-Brain Barrier Damage Can Be Abrogated Using Anti-TNF Treatment

Wilson, Christy; Gaber, M. Waleed; Sabek, Omaima; Zawaski, Janice A.; Merchant, Thomas E.

doi:10.1016/j.ijrobp.2009.02.035

Cited by 131 publications

(106 citation statements)

References 34 publications

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“…Anti-TNF treatment reduced astrogliosis and decreased BBB permeability in irradiated mice [61]. This finding positively correlates with study results showing that TNFnegatively impacts BBB status and increases astrogliosis [45], suggesting that anti-TNF treatment might show benefit in ALS.…”

Section: Potential Therapeutic Strategiessupporting

confidence: 84%

Untitled

2016

NRTOA

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Section: Potential Therapeutic Strategiessupporting

confidence: 84%

Untitled

2016

NRTOA

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“…A previous study on patients who underwent whole-brain radiotherapy demonstrated that this procedure may increase the permeability of the blood-brain barrier and eventually lead to a change in the erlotinib concentration in the cerebrospinal fluid (11). In this study, the plasma and cerebrospinal fluid concentration of erlotinib was measured in six patients with brain metastases from non-small-cell lung cancer who had not undergone whole-brain radiotherapy.…”

Section: Introductionmentioning

confidence: 95%

The concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung cancer

Deng

Feng

et al. 2013

Molecular and Clinical Oncology

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Abstract. It has been demonstrated that erlotinib is effective in treating patients with brain metastasis from non-small-cell lung cancer. However, the number of studies determining the erlotinib concentration in these patients is limited. The purpose of this study was to measure the concentration of erlotinib in the cerebrospinal fluid of patients with brain metastasis from non-small-cell lung carcinoma. Six patients were treated with the standard recommended daily dose of erlotinib (150 mg) for 4 weeks. All the patients had previously received chemotherapy, but no brain radiotherapy. At the end of the treatment period, blood plasma and cerebrospinal fluid samples were collected and the erlotinib concentration was determined by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS̸MS). The average erlotinib concentration in the blood plasma and the cerebrospinal fluid was 717.7±459.7 and 23.7±13.4 ng/ml, respectively. The blood-brain barrier permeation rate of erlotinib was found to be 4.4±3.2%. In patients with partial response (PR), stable disease (SD) and progressive disease (PD), the average concentrations of erlotinib in the cerebrospinal fluid were 35.5±19.0, 19.1±8.7 and 16.4±5.9 ng/ml, respectively. In addition, the efficacy rate of erlotinib for metastatic brain lesions was 33.3%, increasing to 50% in patients with EGFR mutations. However, erlotinib appeared to be ineffective in cases with wild-type EGFR. In conclusion, a relatively high concentration of erlotinib was detected in the cerebrospinal fluid of patients with brain metastases from non-small-cell lung cancer. Thus, erlotinib may be considered as a treatment option for this patient population.

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“…Nonetheless, its effect on the tumor local microenvironment has received less attention. In the brain, irradiation has been shown to cause gliosis through the disruption of the blood brain barrier and the release of inflammatory factors by microglia (8,9). In breast cancer patients who have received focal irradiation, fibrosis and tissue stiffening have been shown to promote tumor cell growth and invasiveness (10).…”

Section: Blood Vessel Formation In Glioblastoma Multiformementioning

confidence: 99%