title: Effects of Copper Reduction on Angiogenesis-Related Factors
  in Recurrent Glioblastoma Cases
abstract: Purposeː To evaluate the therapeutic effects of copper reduction on angiogenesis-related factors in patients with
  glioblastoma multiforme treated by gamma knife radiosurgery. Materials and Methodsː In the present block randomized,
  placebo-controlled trial, fifty eligible patients with a diagnosis of glioblastoma multiforme who were candidates for
  gamma knife radiosurgery were randomly assigned into two groups to receive daily either 1gr penicillamine and a low
  copper diet or placebo for three months. The intervention started on the same day as gamma knife radiosurgery. Serum
  interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF) and copper levels
  were measured at baseline and after the intervention. The serum copper level was used as the final index of compliance
  with the diet. In order to control probable side effects of intervention, laboratory tests were conducted at the beginning,
  middle and end of the study. Resultsː The patients had a mean age and Karnofsky Performance Scale of 43.7 years
  and 75 respectively. Mean serum copper levels were significantly reduced in intervention group. Mean survival time
  was 18.5 months in intervention group vs. 14.9 in placebo group. VEGF and IL-6 levels in the intervention group
  were also significantly reduced compared to the placebo group and TNF-α increased less. Conclusionsː It seems that
  reducing the level of copper in the diet and dosing with penicillamine leads to decline of angiogenesis-related factors
  such as VEGF, IL-6 and TNF-α. Approaches targeting angiogenesis may improve survival and can be used as a future
  therapeutic strategy.
authors.affiliation: Department of Nutrition, School of Public Health, Iran University of Medical Sciences,Tehran, Iran. Email: mhosseinzadeh@tums.ac.ir
authors.forename: Shima
authors.initials: Sh
authors.lastname: Jazayeri
authors.forename: Alireza
authors.initials: A
authors.lastname: Feli
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Bitaraf
authors.forename: Masoud
authors.initials: M
authors.lastname: Solaymani Dodaran
authors.forename: Mazdak
authors.initials: M
authors.lastname: Alikhani
authors.forename: Mohammad Javad
authors.initials: MJ
authors.lastname: Hosseinzadeh-Attar
keywords: Angiogenesis; copper; gamma knife; glioblastoma