Francis Ali-Osman

Positions:

Margaret Harris and David Silverman Professor of Neuro-Oncology Research

Neurosurgery, Neuro-Oncology
School of Medicine

Professor Emeritus in Neurosurgery

Neurosurgery, Neuro-Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

D.Sc. 1982

Free University of Berlin (Germany)

Grants:

P53-dependent GSTP1 Gene Regulation and Glioma Drug Resistance

Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Protein Kinase C and GSTP1 interactions in glioma drug resistance

Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Publications:

Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study.

BACKGROUND: The Mono-amine oxidase-A (MAO-A) enzyme is involved in the degradation and regulation of catecholamines such as serotonin, dopamine, epinephrine and nor-epinephrine. Preclinical studies suggest that this enzyme may contribute to an environment favorable for growth of malignant glioma. The MAO-A gene is located on the X-chromosome and has at least one functional genetic polymorphism. The aim of the present study was to explore possible effects of MAO-A genotype on development of glioblastoma in males. METHODS: Genotypes for 437 glioma cases and 876 population-based controls from the Swedish Glioma International Case-Control study (GICC) were compared. We analyzed the germline DNA using the Illumina Oncoarray. We selected seven single nucleotide polymorphisms (SNPs) located in the MAO-A gene, and imputed genotypes based on data from the 1000 genomes project. We used 1579 male glioblastoma cases and 1875 controls comprising the whole GICC cohort for subsequent validation of findings. RESULTS: The rs144551722 SNP was a significant predictor of development of glioblastoma in males (p-value = 0.0056) but not in females even after correction for multiple testing. We conducted haplotype analysis to confirm an association between MAO-A gene and risk of glioblastoma (p-value = 0.016). We found similar results in the validation sample. CONCLUSIONS: These results suggest the possibility of a role for the MAO-A enzyme and the MAO-A gene in the development of glioblastoma in males.
Authors
Sjöberg, RL; Wu, WY-Y; Dahlin, AM; Tsavachidis, S; Gliogene Group,; Bondy, ML; Melin, B
MLA Citation
Sjöberg, Rickard L., et al. “Role of monoamine-oxidase-A-gene variation in the development of glioblastoma in males: a case control study.J Neurooncol, vol. 145, no. 2, Nov. 2019, pp. 287–94. Pubmed, doi:10.1007/s11060-019-03294-w.
URI
https://scholars.duke.edu/individual/pub1422306
PMID
31556016
Source
pubmed
Published In
J Neurooncol
Volume
145
Published Date
Start Page
287
End Page
294
DOI
10.1007/s11060-019-03294-w

Application of mutagen sensitivity assay in a glioma case-control study.

Few risk factors for glioma have been identified other than ionizing radiation. The alkylating agent acrylamide is a compound found in both occupational and the general environment and identified as one of the forty known or suspected neurocarcinogens in animal models. The mutagen sensitivity assay (MSA) has been used to indirectly show reduced DNA repair capacity upon exposure to ionizing radiation in those with glioma compared to controls. In this study, MSA was used to assess its applicability to a glioma case-control study and to test the hypothesis that subjects with glioma may have lower DNA repair capacity after exposure to selected potential human neurocarcinogens (i.e. acrylamide), compared to controls. Approximately 50 case and 50 control subjects were identified from a clinic-based study that investigated environmental risk factors for glioma, who completed an exposure survey, and had frozen immortalized lymphocytes available. A total of 50 metaphase spreads were read and reported for each participant. The association of case-control status with MSA for acrylamide, i.e. breaks per spread, was examined by multivariable logistic regression models. The mean number of breaks per slide was similar between hospital-based controls and cases. In addition, case-control status or exposure categories were not associated with the number of breaks per spread. Although the MSA has been shown as a useful molecular epidemiology tool for identifying individuals at higher risk for cancer, our data do not support the hypothesis that glioma patients have reduced DNA repair capacity in response to exposure to acrylamide. Further research is needed before the MSA is utilized in large-scale epidemiological investigations of alkylating agents.
Authors
Erdal, S; McCarthy, BJ; Gurule, N; Berwick, M; Gonzales, E; Byrd, J; Flores, K; Shimek, J; Il'yasova, D; Ali-Osman, F; Bigner, DD; Davis, FG; Leyba, AN; White, KAM
MLA Citation
Erdal, Serap, et al. “Application of mutagen sensitivity assay in a glioma case-control study.Toxicol Rep, vol. 5, 2018, pp. 183–88. Pubmed, doi:10.1016/j.toxrep.2017.12.010.
URI
https://scholars.duke.edu/individual/pub1308221
PMID
29854587
Source
pubmed
Published In
Toxicology Reports
Volume
5
Published Date
Start Page
183
End Page
188
DOI
10.1016/j.toxrep.2017.12.010

Correction

MLA Citation
Correction.” Cancer Science, vol. 104, no. 2, Wiley, Feb. 2013, pp. 274–274. Crossref, doi:10.1111/cas.12109.
URI
https://scholars.duke.edu/individual/pub938438
Source
crossref
Published In
Cancer Science
Volume
104
Published Date
Start Page
274
End Page
274
DOI
10.1111/cas.12109

Association between body mass index and mortality in patients with glioblastoma mutliforme.

PURPOSE: To examine the association between obesity and survival in patients with glioblastoma mutliforme (GBM) METHODS: Using a prospective design, 1,259 patients with previously untreated GBM were recruited between 1991 and 2008. Height and weight were self-reported or abstracted from medical records at study entry and used to calculate body mass index (BMI) [weight (kg)/[height (m)](2). Cox proportional models were used to estimate the risk of death associated with BMI as a continuous variable or categorized using established criteria (normal weight, 18.5-24.9 kg/m(2); overweight, 25.0-29.9 kg/m(2); obese, ≥ 30.0 kg/m(2)). RESULTS: Median follow-up was 40 months, and 1,069 (85%) deaths were observed during this period. For all patients, minimal adjusted analyses indicated no significant association between BMI treated as a continuous variable and survival. Compared with patients with a BMI 18.5-24.9 kg/m(2), the minimally adjusted HR for overall survival was 1.08 (95% CI, 0.94-1.24) for a BMI 25-29.9 kg/m(2) and 1.08 (95% CI, 0.91-28) for a BMI ≥ 30.0 kg/m(2). After additional adjustment for adjuvant therapy, the HR for those with a BMI of 25.0-29.9 kg/m(2) was 1.14 (95% CI, 0.99-1.32) and 1.09 (95% CI, 0.91-1.30) for those with a BMI ≥ 30.0 kg/m(2). No significant interactions were revealed for BMI and any demographic variables. CONCLUSION: BMI was not associated with survival in newly diagnosed and previously untreated patients with GBM. Further research investigating the prognostic significance of alternative, quantitative measures of body habitus, and functional performance are required.
Authors
Jones, LW; Ali-Osman, F; Lipp, E; Marcello, JE; McCarthy, B; McCoy, L; Rice, T; Wrensch, M; Il'yasova, D
MLA Citation
Jones, Lee W., et al. “Association between body mass index and mortality in patients with glioblastoma mutliforme.Cancer Causes Control, vol. 21, no. 12, Dec. 2010, pp. 2195–201. Pubmed, doi:10.1007/s10552-010-9639-x.
URI
https://scholars.duke.edu/individual/pub743968
PMID
20838873
Source
pubmed
Published In
Cancer Causes Control
Volume
21
Published Date
Start Page
2195
End Page
2201
DOI
10.1007/s10552-010-9639-x

EGFR and EGFRvIII attenuate drug-induced apoptosis in glioblastomas via mitochondrial transport and interaction with pro-apoptotic proteins:A novel EGFR/EGFRvIII-mediated mechanism in drug resistance

Authors
Zhu, H; Cao, X; Aldrich, A; Ali-Osman, F; Lo, H-W
URI
https://scholars.duke.edu/individual/pub1149151
Source
wos
Published In
Cancer Research
Volume
69
Published Date