Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation

Valadez, J. Geraldo; Sarangi, Anuraag; Lundberg, Christopher J.; Cooper, Michael K.

doi:10.3791/50865

Cited by 9 publications

(6 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Human glioma that is derived from the neural ectoderm is the most common type of intracranial neoplasm, accounting for more than 50%. Gliomas are classified by the World Health Organization (WHO) and numerically graded (I-IV) for pathologic features of malignancy [1]. Furthermore, glioma is also 1 of the most malignant human brain tumors with high morbidity and low survival rates [2].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

Zhang

et al. 2018

Neurotherapeutics

134

View full text Add to dashboard Cite

The current research was aimed at probing into the role of long noncoding RNA (lncRNA) PVT1 in the pathogenesis of glioma and the regulatory mechanism of PVT1/miR-128-3p/GREM1 network in glioma via regulation of the bone morphogenetic protein (BMP) signaling pathway. Microarray analysis was used for preliminary screening for candidate lncRNAs and mRNAs in glioma tissues. Real-time quantitative polymerase chain reaction, Western blot, MTT assay, flow cytometry, migration and invasion assays, and xenograft tumor model were utilized to examine the influence of the lncRNA PVT1/miR-128-3p/GREM1 network on the biological functions of glioma cells. Luciferase assay and RNA-binding protein immunoprecipitation assay were used to validate the miR-128-3p-target relationships with lncRNA PVT1 or GREM1. In addition, the impact of GREM1 on BMP signaling pathway downstream proteins BMP2 and BMP4 was detected via Western blot. LncRNA PVT1 was highly expressed in human glioma tissues and significantly associated with WHO grade (I-II vs III-IV; p < 0.05). There existed a regulatory relationship between lncRNA PVT1 and miR-128-3p as well as that between miR-128-3p and GREM1. MiR-128-3p was downregulated, whereas GREM1 was upregulated in glioma tissues in comparison with para-carcinoma tissues. Overexpression of GREM1 promoted the proliferation and metastatic potential of glioma cells, whereas miR-128-3p mimics inhibited the glioma cell activity through targeting GREM1. Furthermore, lncRNA PVT1 acted as a sponge of miR-128-3p and, thus, influenced the BMP signaling pathway downstream proteins BMP2 and BMP4 through regulating GREM1. LncRNA PVT1 modulated GREM1 and BMP downstream signaling proteins through sponging miR-128-3p, thereby promoting tumorigenesis and progression of glioma.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED: LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

Zhang

et al. 2018

Neurotherapeutics

134

View full text Add to dashboard Cite

show abstract

“…Gliomas, the most common primary malignant brain tumor, show high recurrence and mortality rates 1 – 4 . Initially, they were categorized into grades I to IV based on the appearance of certain histopathologic characteristics, such as vascular proliferation, mitosis, polymorphism and necrosis 5 . However, these diagnostic criteria were subjective and the consistency among different neuropathologists was poor 6 .…”

Section: Introductionmentioning

confidence: 99%

A new glioma grading model based on histopathology and Bone Morphogenetic Protein 2 mRNA expression

Zhou

Zhao

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Glioma, the most common form of primary malignant brain tumors, is graded based solely on histopathological appearance, which has led to prognostic discrepancies. This study aimed to establish a new glioma grading model by analyzing the expression of Bone Morphogenetic Protein 2 (BMP2) mRNA in patients with gliomas as well, named the Histopathological-BMP2 (HB) system. Clinical information was collected from 692 patients from the Chinese Glioma Genome Atlas database. According to pathological glioma subtypes and the expression of BMP2 mRNA in tumor tissues, the new subtypes HBs, HBh, HBm and HB1 were established, with BMP2 expression highest in HBs and lowest in HB1. Survival periods were analyzed. Based on this, the expression of three BMP2 receptors (BMPR1A, BMPR1B, and BMPR2) was also analyzed, which was related to the prognosis of patients. This new classification model was validated in further groups of patients from the CGGA database (n = 291) and the Cancer Genome Atlas (n = 625). A new glioma grade (HB grade) based on histopathology and BMP2 expression can predict the prognosis of glioma patients, with BMPR1B and BMPR2 expression indicating a different prognosis in different types of gliomas. The higher the concentration of BMP2, the better the prognosis of patients.

show abstract

“…To detect human glioblastoma cells in mouse brain, we used a 1:100 dilution of the mouse anti-vimentin antibody clone V9 (Dako, M0725), which has no cross-reactivity with mouse vimentin ( Valadez et al, 2014 ). We also determined the levels of immune cells positive for CD3-Ɛ using a 1:10 dilution of Armenian Hamster anti-CD3-Ɛ antibody-FITC followed by a 1:100 dilution of the secondary mouse anti-FITC antibody (clone FL-D6, Cat# A1812, Sigma).…”

Section: Methodsmentioning

confidence: 99%

Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug

Sharpe¹,

Livingston²,

Gist³

et al. 2015

EBioMedicine

View full text Add to dashboard Cite

The last major advance in the treatment of glioblastoma multiforme (GBM) was the introduction of temozolomide in 1999. Treatment with temozolomide following surgical debulking extends survival rate compared to radiotherapy and debulking alone. However, virtually all glioblastoma patients experience disease progression within 7 to 10 months. Although many salvage treatments, including bevacizumab, rechallenge with temozolomide, and other alkylating agents, have been evaluated, none of these clearly improves survival. Monoamine oxidase B (MAOB) is highly expressed in glioblastoma cell mitochondria, and mitochondrial function is intimately tied to treatment-resistant glioblastoma progression. These glioblastoma properties provide a strong rationale for pursuing a MAOB-selective pro-drug treatment approach that, upon drug activation, targets glioblastoma mitochondria, especially mitochondrial DNA. MP-MUS is the lead compound in a family of pro-drugs designed to treat GBM that is converted into the mature, mitochondria-targeting drug, P+-MUS, by MAOB. We show that MP-MUS can successfully kill primary gliomas in vitro and in vivo mouse xenograft models.

show abstract

Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation

Cited by 9 publications

References 22 publications

RETRACTED: LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

RETRACTED: LncRNA PVT1 Facilitates Tumorigenesis and Progression of Glioma via Regulation of MiR-128-3p/GREM1 Axis and BMP Signaling Pathway

A new glioma grading model based on histopathology and Bone Morphogenetic Protein 2 mRNA expression

Successful Treatment of Intracranial Glioblastoma Xenografts With a Monoamine Oxidase B-Activated Pro-Drug

Contact Info

Product

Resources

About