title: Hypericin uptake: a prognostic marker for survival in high-grade glioma.
abstract: Currently adjuvant chemotherapy for glioblastoma patients can prolong survival time relative to patients who receive only surgery and radiotherapy. Despite these improvements and experimental and clinical efforts the prognosis for glioblastoma patients remains poor. At present, interest is focused on individual prognostic factors influencing patient responses to therapy. Photodynamic therapy may be a promising therapeutic option in the treatment of glioblastoma. In this investigation we examined whether uptake of hypericin (HY), a fluorescent photosensitization agent, by ex vivo glioblastoma cell lines correlates with prognosis of the individual from which the cell lines were derived. Twelve primary human glioma cell cultures were incubated with 20 micromol HY. Fluorescence intensity was measured using fluorescence microscopy. Three patients suffered from an anaplastic astrocytoma, WHO grade III, nine had a glioblastoma, WHO grade IV. In 6/12 patients complete tumour resection was possible. The mean survival time of the six patients in whom complete tumour resection was performed was 26 months, compared with 5 months for those who underwent incomplete resection. Eleven patients received radiation therapy. The five patients who received chemotherapy survived for a mean duration of 26 months, compared with the seven patients who survived for a mean duration of 5 months without chemotherapy. Statistical analysis using a parametric survival model based on the Weibull distribution showed that fluorescence intensity was the variable with the lowest p-value associated with survival (p=0.0225). An increase of 553 arbitrary units of fluorescence intensity is predicted to double survival time. Uptake of HY, a lipophilic molecule, is assumed to be related to low-density lipoprotein (LDL) uptake and metabolism. Cell proliferation is associated with a high turnover of cholesterol and membrane growth, which is related to cholesterol uptake by LDL. In summary, HY uptake by ex vivo glioblastoma cell cultures seems to be positively associated with survival of patients with malignant glioma.
authors.affiliation: Department of Neurosurgery, University of Tuebingen, Hoppe-Seyler-Str. 3, 72076 Tuebingen, Germany. rainer.ritz@med.uni-tuebingen.de
authors.forename: R
authors.initials: R
authors.lastname: Ritz
authors.forename: M
authors.initials: M
authors.lastname: Müller
authors.forename: K
authors.initials: K
authors.lastname: Dietz
authors.forename: F
authors.initials: F
authors.lastname: Duffner
authors.forename: A
authors.initials: A
authors.lastname: Bornemann
authors.forename: F
authors.initials: F
authors.lastname: Roser
authors.forename: M
authors.initials: M
authors.lastname: Tatagiba
mesh_terms: D000328:Adult; D000368:Aged; D000873:Anthracenes; D001254:Astrocytoma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D004358:Drug Therapy; D005260:Female; D005453:Fluorescence; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008027:Light; D008077:Lipoproteins, LDL / Q000378:metabolism; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D008875:Middle Aged; D015233:Models, Statistical; D010569:Perylene / Q000031:analogs & derivatives* / Q000378:metabolism; D010778:Photochemotherapy / Q000379:methods* / Q000592:standards; D011237:Predictive Value of Tests; D011379:Prognosis; D011838:Radiation-Sensitizing Agents / Q000378:metabolism; D011878:Radiotherapy; D015996:Survival Rate
chemical_list: D000873:Anthracenes; D008077:Lipoproteins, LDL; D011838:Radiation-Sensitizing Agents; D010569:Perylene; C004965:hypericin