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

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

Protein Kinase C and GSTP1 interactions in glioma drug resistance

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

NCI Howard Temin Award (K01) Transition

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Novel Targeted Therapeutics for CNS Malignancies

Administered By
Surgery, Surgical Sciences
Awarded By
National Institutes of Health
Role
Collaborating Investigator
Start Date
End Date

Research Training In Neuro-Oncology

Administered By
Neurosurgery, Neuro-Oncology
Awarded By
National Institutes of Health
Role
Mentor
Start Date
End Date

Publications:

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

Identification and functional characterization of the human glutathione S-transferase P1 gene as a novel transcriptional target of the p53 tumor suppressor gene.

The glutathione S-transferase P1 (GSTP1) is involved in multiple cellular functions, including phase II metabolism, stress response, signaling, and apoptosis. The mechanisms underlying the significantly high GSTP1 expression in many human tumors are, however, currently not well understood. We report here that the GSTP1 gene is a heretofore unrecognized downstream transcriptional target of the tumor suppressor p53. We identified a p53-binding motif comprising two consecutive half-sites located in intron 4 of the GSTP1 gene and is highly homologous to consensus p53-binding motifs in other p53-responsive genes. Using a combination of electrophoretic mobility shift assay and DNase I footprinting analyses, we showed that wild-type p53 protein binds to the GSTP1 p53 motif and luciferase reporter assays showed the motif to be transcriptionally functional in human tumor cells. In a temperature-sensitive p53-mutant cells, levels of both p21/WAF1 and GSTP1 gene transcripts increased time dependently when cells were switched from the inactive mutant state to the wild-type p53 state. Small interfering RNA-mediated reduction of p53 expression resulted in a specific decrease in GSTP1 expression and in tumor cells with mutated p53; adenovirally mediated expression of wild-type p53 increased GSTP1 expression significantly. In a panel of early-passage brain tumor cultures from patients, high levels of GSTP1 transcripts and protein were associated with wild-type p53 and, conversely, low GSTP1 levels with mutant p53. p53 expression knockdown by small interfering RNA increased cisplatin sensitivity. The ability of wild-type p53 to transcriptionally activate the human GSTP1 gene defines a novel mechanism of protecting the genome and, potentially, of tumor drug resistance.
Authors
Lo, H-W; Stephenson, L; Cao, X; Milas, M; Pollock, R; Ali-Osman, F
MLA Citation
Lo, Hui-Wen, et al. “Identification and functional characterization of the human glutathione S-transferase P1 gene as a novel transcriptional target of the p53 tumor suppressor gene..” Mol Cancer Res, vol. 6, no. 5, May 2008, pp. 843–50. Pubmed, doi:10.1158/1541-7786.MCR-07-2105.
URI
https://scholars.duke.edu/individual/pub700934
PMID
18505928
Source
pubmed
Published In
Molecular Cancer Research : Mcr
Volume
6
Published Date
Start Page
843
End Page
850
DOI
10.1158/1541-7786.MCR-07-2105