Transfer of this CIDA to Vanderbilt University is requested to allow collaboration with the sponsor. Dr. Harold Moses. Preliminary data demonstrate an association between cell surface immunophenotype with the karyotype, histopathologic grade of malignant glioma and the duration of clinical survival. It is hypothesized that cell surface antigenic events provide a selective advantage to the expressing neoplasm in association with immunosuppression and/or proliferative stimulation. The mechanism(s) of the latter probably involve growth factors (GF). To further understand the significance of the transformation-related immunophenotypic changes observed, this application proposes to: (1) To determine whether the elements for an autocrine loop exists, the production or absence of the mRNA's and protein products of transforming growth factor-beta (TGF- b1,2,3), transforming growth factor-alpha (TGF-a), epidermal growth factor (EGF), platelet derived growth factor (PDGF), and their respective receptors (where available) will be established among malignant glioma cultures; (2) To correlate the expression of stimulatory GF with clinical, pathologic grade and experimental parameters (the cytogenetic and immunophenotypic abnormalities). Differential expression of GF may provide insights into the sequence of stage-related abnormalities of glioma progression. Additionally, the presence of putatively immunosuppressive TGF-b family gene products will be correlated with the immunophenotypic complexity of the cultures, as well as with the duration of the clinical survival of affected patients; (3) Determine whether a limited number of original biopsies (where available as well as of newly resected primary and recurrent CNS neoplasms (5-10) demonstrate the expression of similar GF/GF- receptor, and immunophenotypic (with a more restricted panel of antigens) correlations EX VIVO as identified IN VITRO. This portion of the investigation will be directed by the findings in 1 and 2. Tumors will be examined by Northern and Southern blot analysis, in situ hybridization and immunocytochemistry for TGF-a/EGF, EGF-R, PDGF, and TGF-b1,2,3.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
2K08NS000986-05A1
Application #
3083595
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1985-07-01
Project End
1991-11-30
Budget Start
1990-04-01
Budget End
1990-11-30
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
Jennings, M T; Kaariainen, I T; Gold, L et al. (1994) TGF beta 1 and TGF beta 2 are potential growth regulators for medulloblastomas, primitive neuroectodermal tumors, and ependymomas: evidence in support of an autocrine hypothesis. Hum Pathol 25:464-75
Jennings, M T; Slatkin, N; D'Angelo, M et al. (1993) Neoplastic meningitis as the presentation of occult primitive neuroectodermal tumors. J Child Neurol 8:306-12
Johnson, M D; Jennings, M T; Gold, L I et al. (1993) Transforming growth factor-beta in neural embryogenesis and neoplasia. Hum Pathol 24:457-62
Jennings, M T; Jennings, D L; Ebrahim, S A et al. (1992) In vitro karyotypic and immunophenotypic characterisation of primitive neuroectodermal tumours: similarities to malignant gliomas. Eur J Cancer 28A:762-6
Jennings, M T; Maciunas, R J; Carver, R et al. (1991) TGF beta 1 and TGF beta 2 are potential growth regulators for low-grade and malignant gliomas in vitro: evidence in support of an autocrine hypothesis. Int J Cancer 49:129-39
Jennings, M T; Asadourian, L L; Jennings, V D et al. (1990) Factor analysis of the immunophenotypes of astrocytomas and malignant gliomas: correlations with tumor grade and patient survival. J Neurooncol 9:265-73
Jennings, M T; Jennings, V D; Asadourian, L L et al. (1989) Five novel cell surface antigens of CNS neoplasms. J Neurol Sci 89:63-78
Jennings, M T; Jennings, V D; Asadourian, L L et al. (1989) Antigenic phenotypes of cultured malignant astrocytomas: identification of lineage-consistent, lineage-independent and putative tumor-restricted antigenic expression. J Neurol Sci 89:79-92