Lentiviral Vector Induced Modeling of High-Grade Spinal Cord Glioma in Minipigs

High-grade spinal cord gliomas are rare and carry a poor prognosis. A number of treatment modalities exist for spinal cord gliomas, but no consensus exists regarding their management. Cordectomy represents a possible option for treating these lesions; however, few cases have been reported in adults, and none have been reported in the pediatric population. The authors describe the use of cordectomy for the treatment of a high-grade spinal glioma in a 9-year-old boy who remains cancer free 14 years following his initial presentation.

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Treatment Outcome of High-grade Spinal Cord Glioma

Spinal Surgery ◽

10.2531/spinalsurg.27.270 ◽

2013 ◽

Vol 27 (3) ◽

pp. 270-273

Author(s):

Toshitaka Seki ◽

Kazutoshi Hida ◽

Shunsuke Yano ◽

Takeshi Aoyama ◽

Izumi Koyanagi ◽

...

Keyword(s):

Spinal Cord ◽

Treatment Outcome ◽

High Grade ◽

Spinal Cord Glioma

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Lentiviral-Induced Spinal Cord Gliomas in Rat Model

International Journal of Molecular Sciences ◽

10.3390/ijms222312943 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12943

Author(s):

Purva P. Nagarajan ◽

Muhibullah S. Tora ◽

Stewart G. Neill ◽

Thais Federici ◽

Pavlos Texakalidis ◽

...

Keyword(s):

Spinal Cord ◽

Rat Model ◽

Lentiviral Vector ◽

Treatment Options ◽

High Grade Glioma ◽

Proliferation Index ◽

Positive Staining ◽

High Grade ◽

Intramedullary Spinal Cord ◽

Poor Treatment

Intramedullary spinal cord tumors are a rare and understudied cancer with poor treatment options and prognosis. Our prior study used a combination of PDGF-B, HRAS, and p53 knockdown to induce the development of high-grade glioma in the spinal cords of minipigs. In this study, we evaluate the ability of each vector alone and combinations of vectors to produce high-grade spinal cord gliomas. Eight groups of rats (n = 8/group) underwent thoracolumbar laminectomy and injection of lentiviral vector in the lateral white matter of the spinal cord. Each group received a different combination of lentiviral vectors expressing PDGF-B, a constitutively active HRAS mutant, or shRNA targeting p53, or a control vector. All animals were monitored once per week for clinical deficits for 98 days. Tissues were harvested and analyzed using hematoxylin and eosin (H&E) and immunohistochemical (IHC) staining. Rats injected with PDGF-B+HRAS+sh-p53 (triple cocktail) exhibited statistically significant declines in all behavioral measures (Basso Beattie Bresnahan scoring, Tarlov scoring, weight, and survival rate) over time when compared to the control. Histologically, all groups except the control and those injected with sh-p53 displayed the development of tumors at the injection site, although there were differences in the rate of tumor growth and the histopathological features of the lesions between groups. Examination of immunohistochemistry revealed rats receiving triple cocktail displayed the largest and most significant increase in the Ki67 proliferation index and GFAP positivity than any other group. PDGF-B+HRAS also displayed a significant increase in the Ki67 proliferation index. Rats receiving PDGF-B alone and PDGF-B+ sh-p53 displayed more a significant increase in SOX2-positive staining than in any other group. We found that different vector combinations produced differing high-grade glioma models in rodents. The combination of all three vectors produced a model of high-grade glioma more efficiently and aggressively with respect to behavioral, physiological, and histological characteristics than the rest of the vector combinations. Thus, the present rat model of spinal cord glioma may potentially be used to evaluate therapeutic strategies in the future.

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GLT1 gene delivery based on bone marrow-derived cells ameliorates motor function and survival in a mouse model of ALS

Scientific Reports ◽

10.1038/s41598-021-92285-x ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Natsuko Ohashi ◽

Tomoya Terashima ◽

Miwako Katagi ◽

Yuki Nakae ◽

Junko Okano ◽

...

Keyword(s):

Spinal Cord ◽

Gene Therapy ◽

Bone Marrow ◽

Mouse Model ◽

Lentiviral Vector ◽

White Blood Cells ◽

Glutamate Toxicity ◽

Pathological Lesion ◽

Arginase 1 ◽

Therapy Strategy

AbstractAmyotrophic lateral sclerosis (ALS) is an intractable neurodegenerative disease. CD68-positive bone marrow (BM)-derived cells (BMDCs) accumulate in the pathological lesion in the SOD1(G93A) ALS mouse model after BM transplantation (BMT). Therefore, we investigated whether BMDCs can be applied as gene carriers for cell-based gene therapy by employing the accumulation of BMDCs. In ALS mice, YFP reporter signals were observed in 12–14% of white blood cells (WBCs) and in the spinal cord via transplantation of BM after lentiviral vector (LV) infection. After confirmation of gene transduction by LV with the CD68 promoter in 4–7% of WBCs and in the spinal cord of ALS mice, BM cells were infected with LVs expressing glutamate transporter (GLT) 1 that protects neurons from glutamate toxicity, driven by the CD68 promoter, which were transplanted into ALS mice. The treated mice showed improvement of motor behaviors and prolonged survival. Additionally, interleukin (IL)-1β was significantly suppressed, and IL-4, arginase 1, and FIZZ were significantly increased in the mice. These results suggested that GLT1 expression by BMDCs improved the spinal cord environment. Therefore, our gene therapy strategy may be applied to treat neurodegenerative diseases such as ALS in which BMDCs accumulate in the pathological lesion by BMT.

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Canine spinal cord glioma

Journal of Veterinary Diagnostic Investigation ◽

10.1177/1040638716673127 ◽

2016 ◽

Vol 29 (1) ◽

pp. 126-132 ◽

Cited By ~ 5

Author(s):

Daniel R. Rissi ◽

Renee Barber ◽

Annabelle Burnum ◽

Andrew D. Miller

Keyword(s):

Spinal Cord ◽

Spinal Cord Glioma

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HGG-12. A CASE OF PEDIATRIC SPINAL HIGH-GRADE GLIOMA WITH NTRK1 GENE FUSION

Neuro-Oncology ◽

10.1093/neuonc/noaa222.301 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii346-iii346

Author(s):

Tamaki Morisako ◽

Daisuke Umebayashi ◽

Kazuaki Kamata ◽

Hiroyuki Yamamoto ◽

Takumi Yamanaka ◽

...

Keyword(s):

Spinal Cord ◽

Mr Imaging ◽

Tumor Progression ◽

Gene Fusion ◽

High Grade Glioma ◽

Gene Panel ◽

Partial Resection ◽

Low Grade ◽

High Grade ◽

Surgical Specimen

Abstract INTRODUCTION Tumors arising from the spinal cord are uncommon, especially high-grade tumors in pediatric patients. We report a case of high-grade glioma in the spinal cord harboring NTRK1 gene fusion, who received effective entrectinib therapy. CASE REPORT: A 5-year-old boy presented right hemiparesis and MR imaging revealed an intramedullary enhancing mass at the vertebral body level between C3 and Th1. He underwent microsurgical partial resection and the histological diagnosis was low-grade astrocytoma. After the first-line chemotherapy with vincristine and carboplatin, his right hemiparesis deteriorated and recurrent MR imaging showed growth of the tumor. He underwent microsurgical partial resection again and the histological examination was high-grade glioma with endothelial proliferation and necrosis. The chemoradiotherapy with temozolomide and focal irradiation of 50.4 Gy were given, and his neurological symptom slightly improved. One month later, he presented respiratory disturbance and required assisted ventilation with tracheostomy. MR imaging showed tumor progression invading upward to medulla oblongata. NTRK1 gene fusion was detected in the previous surgical specimen by a gene panel testing, and he received entrectinib, a potent inhibitor of tropomyosin receptor kinase (TRK). Since then, no tumor progression has been demonstrated for several months by MRI and he has been stable neurologically. CONCLUSION High-grade spinal cord tumors are rare and effective treatment strategies have not been addressed. Although the frequency of the gene fusion is very low in pediatric gliomas, identification of the driver gene aberration like in this case by a gene panel can provide potential targeted therapies for selected patients.

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Irradiation of Pediatric High-Grade Spinal Cord Tumors

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2009.09.071 ◽

2010 ◽

Vol 78 (5) ◽

pp. 1451-1456 ◽

Cited By ~ 24

Author(s):

Rahul D. Tendulkar ◽

Atmaram S. Pai Panandiker ◽

Shengjie Wu ◽

Larry E. Kun ◽

Alberto Broniscer ◽

...

Keyword(s):

Spinal Cord ◽

High Grade ◽

Spinal Cord Tumors

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Repeat decompression surgery for recurrent spinal metastases

Journal of Neurosurgery Spine ◽

10.3171/2010.3.spine08670 ◽

2010 ◽

Vol 13 (1) ◽

pp. 109-115 ◽

Cited By ~ 23

Author(s):

Ilya Laufer ◽

Andrew Hanover ◽

Eric Lis ◽

Yoshiya Yamada ◽

Mark Bilsky

Keyword(s):

Spinal Cord ◽

Survival Time ◽

Median Survival ◽

Spinal Cord Compression ◽

Median Survival Time ◽

Eastern Cooperative Oncology Group ◽

Cord Compression ◽

Decompression Surgery ◽

High Grade

Object In this paper, the authors' goal was to determine the outcome of reoperation for recurrent epidural spinal cord compression in patients with metastatic spine disease. Methods A retrospective chart review was conducted of all patients who underwent spine surgery at the Memorial Sloan-Kettering Cancer Center between 1996 and 2007. Thirty-nine patients who underwent reoperation of the spine at the level previously treated with surgery were identified. Only patients whose reoperation was performed because of tumor recurrence leading to high-grade epidural spinal cord compression or recurrence with no further radiation options were included in the study. Patients who underwent reoperations exclusively for instrumentation failure were excluded. All patients underwent additional decompression via a posterolateral approach without removal of the spinal instrumentation. Results Patients underwent 1–4 reoperations at the same level. A median survival time of 12.4 months was noted after the first reoperation, and a median survival time of 9.1 months was noted after the last reoperation. At last follow-up 22 (65%) of 34 patients were ambulatory at the time of last follow-up or death, and the median time between loss-of-ambulation and death was 1 month. Functional status was maintained or improved by one Eastern Cooperative Oncology Group grade in 97% of patients. A major surgical complication rate of 5% was noted. Conclusions Reoperation represents a viable option in patients with high-grade epidural spinal cord compression who have recurrent metastatic tumors at previously operated spinal levels. In carefully selected patients, reoperation can prolong ambulation and result in good functional and neurological outcomes.

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