Radiation Biology

PV QA 1 - Poster Viewing Q&A 1

SU_36_2358 - Intrinsic Resistance of V-SVZ Neural Stem Cells Subjected to Concurrent Daily Radiation and Temozolomide Therapy

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Intrinsic Resistance of V-SVZ Neural Stem Cells Subjected to Concurrent Daily Radiation and Temozolomide Therapy
B. Cameron1, G. Traver2, M. L. Freeman1, J. Wang2, K. Sekhar3, L. Johnson2, D. Dean2, and M. Fahhoum2; 1Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, 2Vanderbilt University Medical Center, Nashville, TN, 3Vanderbilt University Medical Center, Nashvville, TN

Purpose/Objective(s): Neural stem cells (NSCs) in the adult brain reside in niches termed the V-SVZ and SGZ. Emerging research suggests that adult V-SVZ NSCs can transform into malignant astrocytomas that are highly resistant to therapy. Additionally, clinical evidence suggests that glioblastoma contacting the V-SVZ is highly resistant to chemoradiation. An important question is the origin of this resistance. The majority of NSCs (GFAP+/SOX2+ B cells) that populate the V-SVZ are quiescent. We hypothesized that malignant astrocytoma therapeutic resistance is based, in part, on an intrinsic resistance of quiescent NSC B cells.

Materials/Methods: Cohorts of 10-12 week old C57Bl6 male and female mice were injected with 0 or 50 mg/kg temozolomide ip 1 hr prior to administration of 0 or 2 Gy (300 kVp/10mA X-rays) whole brain radiation daily for five days. Mice were sacrificed 24 hours after the 5th dose of radiation or 14 days later injected with 0 or 100 mg/kg TMZ for another 5 days and then sacrificed after 60 days. At sacrifice mice were transcardially perfused and brains fixed. Serial 10 μm sections were collected throughout the SVZ. Sections were stained for stem cells markers including GFAP and SOX-2. Immunofluorescent Jpeg images were capture using an Apiro Versa 200 or an Olympus FV-1000 inverted confocal microscope and analyzed using Image J (NIH).

Results: Because preclinical literature is sparse regarding the effects of combined daily, fractionated radiation and temozolomide (TMZ) on quiescent NSC B cells, we began by quantifying their response to combined therapy. Ventricles were identified histologically and by SDF1 immunofluorescent ependymal cells that line the ventricles. NSC B cells located along the dorsal and dorsolateral walls of a ventricle were identified by co-expressed SOX2 and GFAP. The number of NSC B cells in female mice present 24 hrs after the last fraction of TMZ and irradiation was not significantly different from sham treated (P =0.54, N= 6 mice, 18 fields). In contrast, there was a 60% increase in NSC B cells in treated male mice (P= 0.0012, N= 6 mice, 17 fields).

Conclusion: The ability of quiescent NSC B cells to survive 5-daily TMZ and irradiation treatments suggests that these cells may be intrinsically resistant. We will report on whether B cells are resistant 80 days after treatment.

Author Disclosure: B. Cameron: None. G. Traver: None. M.L. Freeman: None. J. Wang: None.

Brent Cameron, MD, PhD

Vanderbilt University Medical Center

Presentation(s):

Send Email for Brent Cameron


Assets

SU_36_2358 - Intrinsic Resistance of V-SVZ Neural Stem Cells Subjected to Concurrent Daily Radiation and Temozolomide Therapy



Attendees who have favorited this

Please enter your access key

The asset you are trying to access is locked. Please enter your access key to unlock.

Send Email for Intrinsic Resistance of V-SVZ Neural Stem Cells Subjected to Concurrent Daily Radiation and Temozolomide Therapy