scholarly journals Iroquois transcription factors are perturbed in diffuse intrinsic pontine glioma.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Brain Cancer ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Differentially Expressed ◽  
Normal Brain ◽  
Pontine Glioma ◽  
Control Brain ◽  
Cancer Transcriptome ◽  
Tissue Of Origin ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
The Brain

The brain cancer diffuse intrinsic pontine glioma (DIPG) is the most fatal of all cancers with a 5-year survival rate of less than 1%, meaning greater than 99% of patients diagnosed with DIPG will expire within 5 years (1). Systems-level analyses of the cancer transcriptome compared to the tissue from which it arises presents a unique opportunity to gain insights into the transcriptional behavior of each cancer and how it differs from its tissue of origin (2). In this study I used published microarray data to compare the DIPG tumor transcirptomes to that of the normal brain (3). In both datasets, I found differential expression of an Iroquois transcription factor in DIPG tumors: in one dataset, IRX2, IRX5 and IRX3 were among the most differentially expressed genes in the tumors of patients with DIPG, and in a separate dataset, IRX4 was significantly differentially expressed when compared to control brain tissues. IRX proteins may be important molecules in the biology of diffuse intrinsic pontine gliomas.

scholarly journals In diffuse intrinsic pontine gliomas, non-coding RNA expression is significantly varied dependent on overall survival

2021 ◽  
Author(s):  
Rucha ◽  
Vijay S
Keyword(s):  
Overall Survival ◽  
Brain Cancer ◽  
Transcriptional Activity ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Rna Expression ◽  
Pontine Glioma ◽  
Non Coding Rna ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
New Treatments ◽  
Pediatric Brain

Abstract Diffuse intrinsic pontine glioma is a kind of pediatric brain cancer that kills 99 percent of patients within five years and for which there are no conventional chemotherapies. It is crucial for new treatments to comprehend the cancer's transcriptional activity. Using a published dataset, we compared the transcriptomes of tumors from patients who lived longer or less than six months. Among the genes whose expression changed most, we observed that numerous microRNAs and snoRNAs were present. The publication's findings are the first evidence of variable levels of non-coding RNA expression in diffuse intrinsic pontine glioma.

scholarly journals Non-coding RNA are differentially expressed in diffuse intrinsic pontine gliomas based on overall survival.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Brain Cancer ◽  
Expression Profiling ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Novel Therapies ◽  
Pontine Glioma ◽  
Non Coding Rna ◽  
Differential Gene ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
Pediatric Brain

Diffuse intrinsic pontine glioma is a pediatric brain cancer; 99% of patients diagnosed with this disease will expire within 5 years (1) and there are no standard chemotherapies available for it (2). Understanding the transcriptional behavior of this cancer is critical for the development of novel therapies. We performed global differential gene expression profiling of tumors from patients with DIPG by comparing the transcriptomes of tumors from those who survived greater or less than six months using a published dataset (3). We found that multiple microRNAs and snoRNAs were among the genes whose expression was most different between those who survived greater or less than six months. This is the first report of outcome-associated differential expression of non-coding RNA in diffuse intrinsic pontine glioma.

scholarly journals In diffuse intrinsic pontine gliomas, non-coding RNA expression is significantly varied dependent on overall survival

2021 ◽  
Author(s):  
Henley Castillo ◽  
Kenzie Mellor ◽  
Amelia-Mae Marks ◽  
Willard L
Keyword(s):  
Overall Survival ◽  
Brain Cancer ◽  
Transcriptional Activity ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Rna Expression ◽  
Pontine Glioma ◽  
Non Coding Rna ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
New Treatments ◽  
Pediatric Brain

Abstract Diffuse intrinsic pontine glioma is a kind of pediatric brain cancer that kills 99 percent of patients within five years and for which there are no conventional chemotherapies. It is crucial for new treatments to comprehend the cancer's transcriptional activity. Using a published dataset, we compared the transcriptomes of tumors from patients who lived longer or less than six months. Among the genes whose expression changed most, we observed that numerous microRNAs and snoRNAs were present. The publication's findings are the first evidence of variable levels of non-coding RNA expression in diffuse intrinsic pontine glioma.

scholarly journals The Long Non-Coding RNA H19 Drives the Proliferation of Diffuse Intrinsic Pontine Glioma with H3K27 Mutation

2021 ◽  
Vol 22 (17) ◽  
pp. 9165
Author(s):  
David Roig-Carles ◽  
Holly Jackson ◽  
Katie F. Loveson ◽  
Alan Mackay ◽  
Rebecca L. Mather ◽  
...  
Keyword(s):  
Large Family ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Locked Nucleic Acid ◽  
Normal Brain ◽  
Pontine Glioma ◽  
Incurable Cancer ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Long Non Coding Rna

Diffuse intrinsic pontine glioma (DIPG) is an incurable paediatric malignancy. Identifying the molecular drivers of DIPG progression is of the utmost importance. Long non-coding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, whose functions have not yet been elucidated in DIPG. Herein, we studied the oncogenic role of the development-associated H19 lncRNA in DIPG. Bioinformatic analyses of clinical datasets were used to measure the expression of H19 lncRNA in paediatric high-grade gliomas (pedHGGs). The expression and sub-cellular location of H19 lncRNA were validated in DIPG cell lines. Locked nucleic acid antisense oligonucleotides were designed to test the function of H19 in DIPG cells. We found that H19 expression was higher in DIPG vs. normal brain tissue and other pedHGGs. H19 knockdown resulted in decreased cell proliferation and survival in DIPG cells. Mechanistically, H19 buffers let-7 microRNAs, resulting in the up-regulation of oncogenic let-7 target (e.g., SULF2 and OSMR). H19 is the first functionally characterized lncRNA in DIPG and a promising therapeutic candidate for treating this incurable cancer.

scholarly journals Characterization of the Blood–Brain Barrier Integrity and the Brain Transport of SN-38 in an Orthotopic Xenograft Rat Model of Diffuse Intrinsic Pontine Glioma

Pharmaceutics ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 399 ◽  
Author(s):  
Catarina Chaves ◽  
Xavier Declèves ◽  
Meryam Taghi ◽  
Marie-Claude Menet ◽  
Joelle Lacombe ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Brain Barrier ◽  
Brain Delivery ◽  
Pontine Glioma ◽  
Anticancer Drug Delivery ◽  
Blood Brain ◽  
The Brain

The blood–brain barrier (BBB) hinders the brain delivery of many anticancer drugs. In pediatric patients, diffuse intrinsic pontine glioma (DIPG) represents the main cause of brain cancer mortality lacking effective drug therapy. Using sham and DIPG-bearing rats, we analyzed (1) the brain distribution of 3-kDa-Texas red-dextran (TRD) or [14C]-sucrose as measures of BBB integrity, and (2) the role of major ATP-binding cassette (ABC) transporters at the BBB on the efflux of the irinotecan metabolite [3H]-SN-38. The unaffected [14C]-sucrose or TRD distribution in the cerebrum, cerebellum, and brainstem regions in DIPG-bearing animals suggests an intact BBB. Targeted proteomics retrieved no change in P-glycoprotein (P-gp), BCRP, MRP1, and MRP4 levels in the analyzed regions of DIPG rats. In vitro, DIPG cells express BCRP but not P-gp, MRP1, or MRP4. Dual inhibition of P-gp/Bcrp, or Mrp showed a significant increase on SN-38 BBB transport: Cerebrum (8.3-fold and 3-fold, respectively), cerebellum (4.2-fold and 2.8-fold), and brainstem (2.6-fold and 2.2-fold). Elacridar increased [3H]-SN-38 brain delivery beyond a P-gp/Bcrp inhibitor effect alone, emphasizing the role of another unidentified transporter in BBB efflux of SN-38. These results confirm a well-preserved BBB in DIPG-bearing rats, along with functional ABC-transporter expression. The development of chemotherapeutic strategies to circumvent ABC-mediated BBB efflux are needed to improve anticancer drug delivery against DIPG.

Neonatal Respiratory Failure Caused by Congenital Diffuse Intrinsic Pontine Glioma

2017 ◽  
Vol 32 (6) ◽  
pp. 533-536 ◽  
Author(s):  
Katie M. Satrom ◽  
Rachel A. Phelan ◽  
Christopher L. Moertel ◽  
H. Brent Clark ◽  
Dana E. Johnson ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Postmortem Examination ◽  
Resonance Imaging ◽  
Pontine Glioma ◽  
Who Grade ◽  
The Family ◽  
Magnetic Resonance Imaging Mri ◽  
The Brain ◽  
Who Grade Iii

The authors present a case of diffuse intrinsic pontine glioma presenting in a newborn with stridor and respiratory distress that progressed to respiratory failure. Magnetic resonance imaging (MRI) of the brain revealed findings compatible with the diagnosis of diffuse intrinsic pontine glioma. The family pursued palliative care and postmortem examination confirmed WHO grade III astrocytoma.

scholarly journals Genes encoding histone proteins are differentially expressed between men and women with diffuse intrinsic pontine glioma and their expression correlates with survival.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Brain Cancer ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Histone Genes ◽  
Histone H4 ◽  
Pontine Glioma ◽  
Histone H2b ◽  
Men And Women ◽  
Genes Encoding ◽  
Pediatric Brain ◽  
Median Survival Rate

Diffuse intrinsic pontine glioma is a pediatric brain cancer and has the lowest median survival rate of all cancers known to man (1). 99% of patients diagnosed with DIPG will expire within 5 years (1). Understanding the transcriptional behavior of tumors in DIPG is critical for the development of novel therapies. In this study, I compared the transcriptomes of tumors from men with DIPG versus that of tumors from women diagnosed with DIPG using a published dataset (2). I found that three histone genes, including HIST1H4C, HIST1H2BD, and HIST1H3D, which encode Histone H4, Histone H2B Type 1D, and Histone H3.1 were among the genes whose expression was most different between the DIPG tumors of men and women. Importantly, the expression level of two of these genes significantly correlated in a linear fashion with the amount of time the patient survived. It has previously been reported that 78% of DIPG tumors contain a mutation in Histone H3.1 (HIST1H3B) (3). This is the first report of differential expression of histone genes in tumors of patients with DIPG.

scholarly journals Repression of RNA message for F-box proteins in the tumors of patients with glioblastoma.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Gene Expression ◽  
Brain Cancer ◽  
Gene Expression Analysis ◽  
Normal Brain ◽  
Significant Differential Expression ◽  
Differential Gene Expression Analysis ◽  
Genes Encoding ◽  
Differential Gene ◽  
The Brain ◽  
Median Survival Rate

Glioblastoma is the most common brain cancer in adults and has a 15 month median survival rate (1, 2). We performed differential gene expression analysis, comparing the glioblastoma transcriptome from 17 patients to the transcriptome of 8 non-affected, “normal” brain samples using a published dataset (3). Three separate genes encoding F-box proteins (4), including FBXW7, FBXO41, and FBXL16 were differentially expressed and at significantly lower levels in the tumors of patients with glioblastoma than in the brain. Significant differential expression of FBXW7, FBXO41 and FBXL16 was also observed in glioblastomas from the REMBRANDT study (5).

Identification of Novel Biologic Targets in the Treatment of Newly Diagnosed Diffuse Intrinsic Pontine Glioma

2012 ◽  
pp. 625-628
Author(s):  
Nathan J. Robison ◽  
Mark W. Kieran
Keyword(s):  
Pi3k Pathway ◽  
Diffuse Intrinsic Pontine Glioma ◽  
Experimental Therapy ◽  
Murine Models ◽  
Newly Diagnosed ◽  
Pontine Glioma ◽  
Molecular Features ◽  
Autopsy Series ◽  
Diffuse Intrinsic Pontine Gliomas ◽  
P53 Inactivation

Overview: Diffuse intrinsic pontine gliomas (DIPGs) carry an extremely poor prognosis. Standard practice has been to base the diagnosis on classic imaging and clinical characteristics and to treat with focal radiation therapy, usually accompanied with experimental therapy. As a result of the desire to avoid upfront biopsy, little has been learned regarding the molecular features of this disease. Findings from several autopsy series have included loss of p53 and PTEN, and amplification of PDGFR. Based on these and other findings, murine models have been generated and provide a new tool for preclinical testing. DIPG biopsy at diagnosis has increasingly become incorporated into national protocols at several centers, bringing the prospect of a better understanding of DIPG biology in the future. Initial analyses of pretreatment tumors cast valuable new light and establish the importance of p53 inactivation and the RTK-PI3K pathway in this disease.

scholarly journals De Novo A-to-I RNA Editing Discovery in lncRNA

Cancers ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 2959
Author(s):  
Domenico Alessandro Silvestris ◽  
Chiara Scopa ◽  
Sara Hanchi ◽  
Franco Locatelli ◽  
Angela Gallo
Keyword(s):  
Rna Editing ◽  
Brain Cancer ◽  
Brain Cortex ◽  
De Novo ◽  
Large Fraction ◽  
Bioinformatic Analysis ◽  
Normal Brain ◽  
Editing Event ◽  
Non Coding Rnas ◽  
The Brain

Background: Adenosine to inosine (A-to-I) RNA editing is the most frequent editing event in humans. It converts adenosine to inosine in double-stranded RNA regions (in coding and non-coding RNAs) through the action of the adenosine deaminase acting on RNA (ADAR) enzymes. Long non-coding RNAs, particularly abundant in the brain, account for a large fraction of the human transcriptome, and their important regulatory role is becoming progressively evident in both normal and transformed cells. Results: Herein, we present a bioinformatic analysis to generate a comprehensive inosinome picture in long non-coding RNAs (lncRNAs), using an ad hoc index and searching for de novo editing events in the normal brain cortex as well as in glioblastoma, a highly aggressive human brain cancer. We discovered >10,000 new sites and 335 novel lncRNAs that undergo editing, never reported before. We found a generalized downregulation of editing at multiple lncRNA sites in glioblastoma samples when compared to the normal brain cortex. Conclusion: Overall, our study discloses a novel layer of complexity that controls lncRNAs in the brain and brain cancer.

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