scholarly journals Lentiviral-Induced Spinal Cord Gliomas in Rat Model

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.

scholarly journals P.137 Use of intravenous fluorescein for intra-operative localization of an intramedullary spinal cord tumour; a technical note

2018 ◽  
Vol 45 (s2) ◽  
pp. S52-S52
Author(s):  
JT Adams ◽  
M Hong ◽  
S Christie ◽  
S Barry
Keyword(s):  
Spinal Cord ◽  
High Grade Glioma ◽  
Technical Note ◽  
Intramedullary Tumor ◽  
High Grade ◽  
Intramedullary Spinal Cord ◽  
Intramedullary Lesion ◽  
Multiple Biopsies ◽  
Spinal Cord Tumours ◽  
Spine Tumour

Background: Localization of intramedullary spine tumors can be difficult. Various intraoperative aids have previously been described, but have limited use due to expense, complexity, and time. Intravenous fluorescein is an inexpensive and safe drug that may be useful in the localization of such tumors. We describe a technical description of the intra-operative use of fluorescein as an aid in the localization of a intramedullary spine tumour. Methods: In this technical report, the authors present a case example of a 56 year old man presenting with a intramedullary tumor at the level of C5/6. Intra-operatively intravenous Fluorescein was administered and the Pentero microscope BLUE™ 400 feature was used to accurately identify the lesion. Multiple biopsies of the fluorescent tissue were taken. Results: After 10 cardiac cycles the fluorescent coloring was isolated to what was thought to be the intramedullary lesion. Our myelotomy was made based on the uptake of this fluorescent coloring and multiple biopsies were taken. Final pathology confirmed this tissue was consistent with a high grade glioma. Conclusions: The use of intravenous fluorescein was a valuable aid in localizing the lesion and minimizing the size of our myelotomy. The use of intravenous fluorescein to localize high grade intramedullary spinal cord tumours appears to be safe, accurate, and inexpensive.

scholarly journals Against the Resilience of High-Grade Gliomas: The Immunotherapeutic Approach (Part I)

2021 ◽  
Vol 11 (3) ◽  
pp. 386
Author(s):  
Alice Giotta Lucifero ◽  
Sabino Luzzi
Keyword(s):  
Monoclonal Antibodies ◽  
Natural Killer ◽  
Immune Escape ◽  
Meta Analysis ◽  
Treatment Options ◽  
High Grade Glioma ◽  
High Grade ◽  
Future Challenges ◽  
Genetic Landscape ◽  
High Grade Gliomas

The resilience of high-grade gliomas (HGGs) against conventional chemotherapies is due to their heterogeneous genetic landscape, adaptive phenotypic changes, and immune escape mechanisms. Innovative immunotherapies have been developed to counteract the immunosuppressive capability of gliomas. Nevertheless, further research is needed to assess the efficacy of the immuno-based approach. The aim of this study is to review the newest immunotherapeutic approaches for glioma, focusing on the drug types, mechanisms of action, clinical pieces of evidence, and future challenges. A PRISMA (Preferred Reporting Items for Systematic Review and Meta-Analysis)-based literature search was performed on PubMed/Medline and ClinicalTrials.gov databases using the keywords “active/adoptive immunotherapy,” “monoclonal antibodies,” “vaccine,” and “engineered T cell.”, combined with “malignant brain tumor”, “high-grade glioma.” Only articles written in English published in the last 10 years were selected, filtered based on best relevance. Active immunotherapies include systemic temozolomide, monoclonal antibodies, and vaccines. In several preclinical and clinical trials, adoptive immunotherapies, including T, natural killer, and natural killer T engineered cells, have been shown to be potential treatment options for relapsing gliomas. Systemic temozolomide is considered the backbone for newly diagnosed HGGs. Bevacizumab and rindopepimut are promising second-line treatments. Adoptive immunotherapies have been proven for relapsing tumors, but further evidence is needed.

Targeted Treatment of Experimental Spinal Cord Glioma With Dual Gene-Engineered Human Neural Stem Cells

Neurosurgery ◽  
2015 ◽  
Vol 79 (3) ◽  
pp. 481-491 ◽  
Author(s):  
Alexander E. Ropper ◽  
Xiang Zeng ◽  
Hariprakash Haragopal ◽  
Jamie E. Anderson ◽  
Zaid Aljuboori ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Growth Rate ◽  
Neural Stem Cells ◽  
Tumor Growth ◽  
Rat Model ◽  
Weight Bearing ◽  
Tumor Growth Rate ◽  
Intramedullary Spinal Cord ◽  
Human Neural Stem Cells

Abstract BACKGROUND There are currently no satisfactory treatments or experimental models showing autonomic dysfunction for intramedullary spinal cord gliomas (ISCG). OBJECTIVE To develop a rat model of ISCG and investigate whether genetically engineered human neural stem cells (F3.hNSCs) could be developed into effective therapies for ISCG. METHODS Immunodeficient/Rowett Nude rats received C6 implantation of G55 human glioblastoma cells (10K/each). F3.hNSCs engineered to express either cytosine deaminase gene only (i.e., F3.CD) or dual genes of CD and thymidine kinase (i.e., F3.CD-TK) converted benign 5-fluorocytosine and ganciclovir into oncolytic 5-fluorouracil and ganciclovir-triphosphate, respectively. ISCG rats received injection of F3.CD-TK, F3.CD, or F3.CD-TK debris near the tumor epicenter 7 days after G55 seeding, followed with 5-FC (500 mg/kg/5 mL) and ganciclovir administrations (25 mg/kg/1 mL/day × 5/each repeat, intraperitoneal injection). Per humane standards for animals, loss of weight-bearing stepping in the hindlimb was used to determine post-tumor survival. Also evaluated were autonomic functions and tumor growth rate in vivo. RESULTS ISCG rats with F3.CD-TK treatment survived significantly longer (37.5 ± 4.78 days) than those receiving F3.CD (21.5 ± 1.75 days) or F3.CD-TK debris (19.3 ± 0.85 days; n = 4/group; P <.05, median rank test), with significantly improved autonomic function and reduced tumor growth rate. F3.DC-TK cells migrated diffusively into ISCG clusters to mediate oncolytic effect. CONCLUSION Dual gene-engineered human neural stem cell regimen markedly prolonged survival in a rat model that emulates somatomotor and autonomic dysfunctions of human cervical ISCG. F3.CD-TK may provide a novel approach to treating clinical ISCG.

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

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.

PATH-41. POLYMORPHOUS LOW-GRADE NEUROEPITHELIAL TUMOR OF THE YOUNG WITH FGFR3-TACC3 FUSION MIMICKING HIGH-GRADE GLIOMA: CASE REPORT AND SERIES OF HIGH-GRADE CORRELATES

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi124-vi124
Author(s):  
Danielle Golub ◽  
Peter C Pan ◽  
Benjamin Liechty ◽  
Cheyanne Slocum ◽  
Tejus Bale ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
High Grade Glioma ◽  
Proliferation Index ◽  
Molecular Profile ◽  
Low Grade ◽  
High Grade ◽  
Molecular Features ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Abstract BACKGROUND Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently-described entity that can occasionally histologically and molecularly mimic high-grade glioma. The histologic and molecular features that predict aggressive behavior in FGFR3-TACC3 altered tumors are unclear. CASES We present a rare case of an indolent neuroepithelial neoplasm in a 59-year-old female with imaging initially suggestive of high-grade glioma and analyze common molecular features between this case and a series of high-grade gliomas. After total resection, pathology of the case patient revealed predominantly low-grade cytomorphology, abundant microcalcifications, unusual neovascularization, and a low proliferation index. The lesion was diffusely CD34 immunoreactive and harbored both an FGFR3-TACC3 fusion and a TERT promoter mutation. Based on the overall histologic and molecular profile, a diagnosis of PLNTY was favored. The patient was thereafter observed without adjuvant therapy with no evidence of progression at 15-month follow-up. In contrast, a series of eight adult patients with glioblastomas harboring FGFR3-TACC3 fusions and correspondingly aggressive clinical courses are also presented. Common molecular findings included IDH-wildtype status, absence of 1p19q codeletion, and CDKN2A loss. TERT promoter mutations and lack of MGMT promoter methylation were also frequently observed. These patients demonstrated a median 15-month overall survival and a 6-month progression-free survival. CONCLUSIONS PLNTY is a rare low-grade entity that can display characteristics of high-grade glioma, particularly in adults. The potential for a unique entity mimicking PLNTY which may act as a precursor lesion for a more malignant phenotype should be considered in cases with FGFR3-TACC3 fusions and other high-grade features.

Magnetic resonance imaging findings and antemortem cytologic diagnosis of intramedullary spinal cord ependymoma in a dog

2021 ◽  
pp. 1-6
Author(s):  
Alexandra M. Gibson ◽  
Michael F. Rosser ◽  
Cintia R. de Oliveira ◽  
Rachel Lampe ◽  
Janice M. Pfeiff ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Fine Needle Aspiration ◽  
Treatment Options ◽  
Young Patients ◽  
Spinal Column ◽  
Needle Aspiration ◽  
Lumbar Region ◽  
Resonance Imaging ◽  
Intramedullary Spinal Cord ◽  
Fine Needle

Abstract CASE DESCRIPTION A 3-year-old 31.1-kg castrated male mixed-breed dog was evaluated because of a 1- to 2-week history of paraparesis, knuckling of the hind feet, and difficulty posturing to urinate or defecate. CLINICAL FINDINGS The dog was paraparetic but weakly ambulatory with a kyphotic posture, a mildly decreased patellar reflex in the right pelvic limb, increased tone in both pelvic limbs, and marked hyperesthesia on paraspinal palpation of the lumbar region. The urinary bladder was enlarged and firm on palpation. Neuroanatomic findings were primarily consistent with localization to the T3-L3 spinal cord segments. Magenetic resonance imaging of the thoracolumbar spinal column revealed a discrete intramedullary spinal cord mass from the cranial aspect of L4 to the middle of L5. The mass was sampled by fine-needle aspiration, and on cytologic evaluation, the suspected diagnosis was an ependymoma. TREATMENT AND OUTCOME Owing to poor prognosis and limited treatment options, the owner elected euthanasia. Postmortem examination of the spinal cord and histologic findings for samples of the mass supported a likely diagnosis of ependymoma. CLINICAL RELEVANCE Ependymoma is a rare neoplasm in dogs but should be considered in young patients with evidence of a tumor in the CNS. Fine-needle aspiration of the spinal cord mass was possible in the dog of this report, and the cytologic findings provided useful diagnostic information.

scholarly journals Genomic Landscape of Intramedullary Spinal Cord Tumors Suggests Distinct Genetic Origins Compared to Intracranial Histopathologic Counterparts

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Tej D Azad ◽  
Ming Zhang ◽  
Rajiv Iyer ◽  
Qing Wang ◽  
Tomas Garzon-Muvdi ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Treatment Options ◽  
Driver Mutations ◽  
Whole Genome ◽  
Spinal Cord Tumors ◽  
Intramedullary Spinal Cord ◽  
Molecular Features ◽  
The Central Nervous System

Abstract INTRODUCTION Intramedullary spinal cord tumors (IMSCTs) are a rare, heterogeneous group of neoplasms with limited treatment options and high rates of morbidity and mortality. Next-generation sequencing has revealed opportunities for targeted therapies of the intracranial counterparts of IMSCT, but little is known about the molecular features of IMSCT. METHODS To better understand the genetic basis of these tumors we performed whole exome sequencing on fifty-one IMSCT and matched germline DNA, including 29 ependymomas, 16 astrocytomas, 4 gangliogliomas,1hemangioblastoma, and 1 oligodendroglioma. Whole-genome sequencing was further performed on 12 IMSCT to discover possible structural variants. RESULTS Though recurrent somatic mutations in IMSCTs were rare, we identified NF2 mutations in 15.7% of tumors (ependymoma, N = 7; astrocytoma, N = 1), RP1 mutations in 5.9% of tumors (ependymoma, N = 3), and ESX1 mutations in 5.9% of tumors (ependymoma, N = 3). We further identified copy number amplifications in CTU1 in 25% of myxopapillary ependymomas. Given the paucity of somatic driver mutations, we further performed whole-genome sequencing of 12 tumors (ependymoma, N = 9; astrocytoma, N = 3). Overall, we observed that IMSCTs with intracranial histologic counterparts did not harbor the canonical mutations associated with their intracranial counterparts (eg glioblastoma). CONCLUSION Our findings suggest that the origin of IMSCTs may be distinct from tumors arising within other compartments of the central nervous system and provides a framework to begin more biologically based therapeutic strategies.

Histopathological and Clinical Differences Between Primary Breast Carcinomas With Neuroendocrine Features and Primary Breast Carcinomas Mimicking Neuroendocrine Features

2019 ◽  
Vol 27 (7) ◽  
pp. 744-752
Author(s):  
Canan Kelten Talu ◽  
Taha Cumhan Savli ◽  
Gulben Erdem Huq ◽  
Cem Leblebici
Keyword(s):  
Tumor Cells ◽  
Lymphovascular Invasion ◽  
Lymphocytic Infiltration ◽  
Growth Patterns ◽  
Proliferation Index ◽  
Positive Staining ◽  
High Grade ◽  
Breast Carcinomas ◽  
Ki 67 ◽  
Clear Cytoplasm

We aimed to determine the histopathological differences between primary breast carcinomas with neuroendocrine features (NEBC) and carcinomas mimicking neuroendocrine features (NEBC-like). Twenty-three cases with NEBC, all showing positive staining for synaptophysin and/or chromogranin-A in ≥50% of tumor cells and 36 cases with NEBC-like (no staining for neuroendocrine [NE] markers but suspicious for NE morphology in terms of solid/trabecular growth patterns) were included in the study. Significant differences were found between the groups in terms of the patients’ ages, histologic/nuclear grade of tumor, lymphovascular invasion, comedo-type ductal carcinoma in situ (DCIS), microcalcification, Ki-67 proliferation index, nuclear shape, and level of peritumoral lymphocytic infiltration. The presence of large-size solid cohesive groups of tumor cells; plasmocytoid, spindle, and/or columnar shapes of tumor cells; and eosinophilic-granular appearance of cytoplasm were mostly noted in the NEBC group. The presence of small- to medium-sized solid cohesive groups of tumor cells; high-grade histologic and nuclear features; clear cytoplasm; and round to ovoid nucleus were mostly noted in the NEBC-like group. No significant differences were found in terms of tumor size, ER/PR/HER2 status, as well as the presence of DCIS, elastosis, extracellular/intracellular mucin, signet ring cells, apocrine features, and accompanying papilloma or ductal ectasia. In conclusion, small- to medium-sized solid cohesive groups of tumor cells, high-grade features, clear cytoplasm, round to ovoid shape of nucleus, lymphovascular invasion, comedo-type DCIS, microcalcification, high level of Ki-67 proliferation index (≥20%), and moderate/strong level of peritumoral lymphocytic infiltration might support non-NE features in breast carcinomas.

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

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Muhibullah S. Tora ◽  
Pavlos Texakalidis ◽  
Stewart Neill ◽  
Jeremy Wetzel ◽  
Rima S. Rindler ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Lentiviral Vector ◽  
High Grade ◽  
Spinal Cord Glioma

Advances in Treatment Options for High-grade Glioma - Current Status and Future Perspectives

2010 ◽  
Vol 5 (1) ◽  
pp. 49 ◽  
Author(s):  
Ryan T Merrell ◽  
Eudocia C Quant ◽  
Patrick Y Wen ◽  
◽  
◽  
...  
Keyword(s):  
Anaplastic Astrocytoma ◽  
Brain Tumours ◽  
Treatment Options ◽  
High Grade Glioma ◽  
Current Status ◽  
High Grade ◽  
Novel Therapies ◽  
Targeted Agents ◽  
Future Perspectives ◽  
Primary Brain Tumours

High-grade gliomas, including glioblastoma, anaplastic astrocytoma, anaplatic oligodendroglioma and anaplastic oligoastrocytoma, account for the majority of malignant primary brain tumours diagnosed in adults. The prognosis for these tumours is poor despite multimodality therapy with surgery, radiation and/or chemotherapy. This review summarises treatment options for high-grade glioma, including standard regimens, targeted agents and novel therapies.

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