Human primary brain tumor cell growth inhibition in serum-free medium optimized for neuron survival.
Glioblastoma is the most common primary brain tumor in adults from which about 15,000 patients die each year in the United States. Despite aggressive surgery, radiotherapy and chemotherapy, median survival remains only 1 year. Here we evaluate growth of primary human brain tumor cells in a defined nutrient culture medium (Neuregen) that was optimized for neuron regeneration. We hypothesized that Neuregen would inhibit tumor cell growth because of its ability to inhibit gliosis in rat brain. Tumor tissue was collected from 18 patients including 10 males and 8 females (mean age 60+/-12 years) who underwent craniotomy for newly diagnosed, histologically confirmed brain tumors. The tissue was shipped overnight in Hibernate transport medium. Tumor cells were isolated and plated in Neurobasal/serum or Neuregen on culture plastic. After 1 week, growth in Neuregen was significantly less in 9/10 glioblastoma multiforme cases, 5/5 meningioma cases and 3/3 cases of brain metastasis. Analysis of deficient formulations of Neuregen and formulations to which selected components were added back implicate no single active component. However, individual cases were sensitive to corticosterone, selenium, ethanolamine, fatty acids and/or antioxidants. Therefore, a defined culture medium that promotes neuron regeneration inhibits the growth of human primary glioblastoma, meningioma and metastatic tumor cells in culture. The possible in vivo efficacy of Neuregen for treatment of brain tumor resections remains to be determined.
Brewer
Gregory J
GJ
Departments of Neurology, Medical Microbiology, Immunology and Cell Biology, Southern Illinois University School of Medicine, Springfield, IL 62794-9626, USA. gbrewer@siumed.edu
LeRoux
Peter D
PD
D000368:Aged; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D018929:Cell Culture Techniques / Q000379:methods / Q000639:trends; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D016895:Culture Media, Serum-Free / Q000737:chemistry / Q000494:pharmacology*; D005227:Fatty Acids / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005938:Glucocorticoids / Q000494:pharmacology / Q000627:therapeutic use; D006131:Growth Inhibitors / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008577:Meningeal Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008579:Meningioma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012643:Selenium / Q000494:pharmacology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D005227:Fatty Acids; D005938:Glucocorticoids; D006131:Growth Inhibitors; D012643:Selenium