scholarly journals Molecular Characterization of AEBP1 at Transcriptional Level in Glioma

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Kuanyu Wang ◽  
Ruoyu Huang ◽  
Xuezhi Tong ◽  
Zhiliang Wang ◽  
Shibin Sun ◽  
...  
Keyword(s):  
Survival Analysis ◽  
Bioinformatics Analysis ◽  
Treatment Protocol ◽  
Transcriptional Level ◽  
Wild Type ◽  
Go Analysis ◽  
Kaplan Meier ◽  
Standardized Treatment ◽  
The Brain

Background. Glioma is the most common malignant tumor of the brain in adult patients. The standardized treatment protocol is based on surgical therapy, supplemented with radiotherapy and chemotherapy. However, the prognosis is still unsatisfied. Chemoresistance is one of the most important reason for the poor prognosis of glioma patients. It has confirmed that glioma stem cell (GSC) is one of the reasons for chemoresistance. Methods. In this study, three datasets (GSE23806, COSMIC, and TCGA) were used to perform the analysis to search for the key genes related to GSC, temozolomide (TMZ) resistance, and prognosis. The key gene for further research was selected by reviewing the previous studies. The selected gene investigated the relation between expression levels and clinical characteristics in both TCGA and CGGA dataset. The bioinformatics analysis was performed by Gene Ontology (GO) analysis. The survival analysis was performed by Kaplan–Meier survival analysis. Results. AE binding protein 1 (AEBP1) was selected for further analysis. AEBP1 was overexpressed in GSCs and TMZ resistance cells. In both TCGA and CGGA dataset, the results showed that the expression level of AEBP1 was increased in glioblastoma (GBM) samples, IDH wild-type samples, and MGMT promoter unmethylated samples. Meanwhile, AEBP1 expression was positively related to several GSC markers. GO analysis showed that AEBP1 was related to immune response, cell adhesion, apoptotic process, inflammatory response, positive regulation of cell proliferation, angiogenesis, response to drug, and response to hypoxia. The survival analysis showed that the overexpressed level of AEBP1 was correlated with short survival time in both glioma and GBM patients. Conclusion. In summary, AEBP1 was related with GSC-induced TMZ resistance. Our study showed that AEBP1 might be an oncogene and a new effective therapeutic target for the treatment of glioma.

scholarly journals Molecular Characterization of AEBP1 at Transcriptional Level in Glioma

2020 ◽  
Author(s):  
Kuanyu Wang ◽  
Ruoyu Huang ◽  
Zhiliang Wang ◽  
Xuezhi Tong ◽  
Chenxing Wu
Keyword(s):  
Survival Analysis ◽  
Bioinformatics Analysis ◽  
Treatment Protocol ◽  
Transcriptional Level ◽  
Glioma Stem Cell ◽  
Wild Type ◽  
Go Analysis ◽  
Short Survival Time ◽  
Kaplan Meier ◽  
Standardized Treatment

Abstract Background: Glioma is the most common malignant tumor of brain in adult patients. The standardized treatment protocol was based on surgical therapy, supplemented with radiotherapy and chemotherapy. However, the prognosis was still unsatisfied. The chemoresistance is one of the most important reason for the poor prognosis of glioma patients. It has confirmed that glioma stem cell (GSC) are one of the reasons for chemoresistance.Methods: In this study three datasets (GSE23806, COSMIC, TCGA) was used to perform the analysis to search for the key genes related to GSC, temozolomide (TMZ) resistance and prognosis. The key gene for further research was selected by reviewing the previous studies. The selected gene was investigated the relation between expression levels and clinical characteristics in both TCGA and CGGA dataset. The bioinformatics analysis was performed by Gene ontology (GO) analysis. The survival analysis was performed by Kaplan–Meier survival analysis. Results: AE binding protein 1 (AEBP1) was selected for further analysis. AEBP1 was overexpressed in GSCs and TMZ resistance cells. In both TCGA and CGGA dataset, the results showed that the expression level of AEBP1 was increased in glioblastoma (GBM) samples, IDH wild-type samples and MGMT promoter unmethylated samples. Meanwhile, AEBP1 expression was positive related with several GSC markers. GO analysis showed that AEBP1 were related with immune response, cell adhesion, apoptotic process, inflammatory response, positive regulation of cell proliferation, angiogenesis, response to drug and response to hypoxia. The survival analysis showed that the overexpressed level of AEBP1 was correlated with short survival time in both glioma and GBM patients. Conclusion: In summary, AEBP1 was related with GSC induced TMZ resistance. Our study showed that AEBP1 might be an oncogene and a new effective therapeutic target for the treatment of glioma.

scholarly journals Isolation and characterization of the SPT2 gene, a negative regulator of Ty-controlled yeast gene expression.

1985 ◽  
Vol 5 (7) ◽  
pp. 1543-1553 ◽  
Author(s):  
G S Roeder ◽  
C Beard ◽  
M Smith ◽  
S Keranen
Keyword(s):  
Gene Product ◽  
Regulatory Region ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Wild Type ◽  
Isolation And Characterization ◽  
Mutant Strains ◽  
Insertion Mutations ◽  
His4 Gene

The his4-917 mutation of Saccharomyces cerevisiae results from the insertion of the Ty element Ty917 into the regulatory region of the HIS4 gene and renders the cell His-. The hist4-912 delta mutant, which carries a solo delta in the 5'-noncoding region of HIS4, is His+ at 37 degrees C but His- at 23 degrees C. Both these mutations interfere with HIS4 expression at the transcriptional level. The His- phenotype of both insertion mutations is suppressed by mutations at the SPT2 locus. The product of the wild-type SPT2 gene apparently represses HIS4 transcription in these mutant strains; this repression is relieved when the SPT2 gene is destroyed by mutation. The repression of transcription by SPT2 presumably results from an interaction between the SPT2+ gene product and Ty or delta sequences. In this paper, we report the cloning and DNA sequence analysis of the wild-type SPT2 gene and show that the gene is capable of encoding a protein of 333 amino acids in length. In addition, we show that a dominant mutation of the SPT2 gene results from the generation of an ochre codon which is presumed to lead to a shortened SPT2 gene product.

Characterization of an epilepsy-associated variant of the human Cl−/HCO3−exchanger AE3

2009 ◽  
Vol 297 (3) ◽  
pp. C526-C536 ◽  
Author(s):  
Gonzalo L. Vilas ◽  
Danielle E. Johnson ◽  
Paul Freund ◽  
Joseph R. Casey
Keyword(s):  
Protein Trafficking ◽  
Specific Inhibitor ◽  
Similar Degree ◽  
Transport Activity ◽  
Wild Type ◽  
Hek 293 ◽  
293 Cells ◽  
The Brain ◽  
Exchange Activity

Anion exchanger 3 (AE3), expressed in the brain, heart, and retina, extrudes intracellular HCO3−in exchange for extracellular Cl−. The SLC4A3 gene encodes two variants of AE3, brain or full-length AE3 (AE3fl) and cardiac AE3 (cAE3). Epilepsy is a heterogeneous group of disorders characterized by recurrent unprovoked seizures that affect about 50 million people worldwide. The AE3-A867D allele in humans has been associated with the development of IGE (IGE), which accounts for ∼30% of all epilepsies. To examine the molecular basis for the association of the A867D allele with IGE, we characterized wild-type (WT) and AE3fl-A867D in transfected human embryonic kidney (HEK)-293 cells. AE3fl-A867D had significantly reduced transport activity relative to WT (54 ± 4%, P < 0.01). Differences in expression levels or the degree of protein trafficking to the plasma membrane did not account for the defect of AE3fl-A867D. Treatment with 8-bromo-cAMP (8-Br-cAMP) increased Cl−/HCO3−exchange activity of WT and AE3fl-A867D to a similar degree, which was abolished by preincubation with the protein kinase A (PKA)-specific inhibitor H89. This indicates that PKA regulates WT and AE3fl-A867D Cl−/HCO3−exchange activity. No difference in Cl−/HCO3−exchange activity was found between cultures of mixed populations of neonatal hippocampal cells from WT and slc4a3−/−mice. We conclude that the A867D allele is a functional (catalytic) mutant of AE3 and that the decreased activity of AE3fl-A867D may cause changes in cell volume and abnormal intracellular pH. In the brain, these alterations may promote neuron hyperexcitability and the generation of seizures.

Isolation and characterization of the SPT2 gene, a negative regulator of Ty-controlled yeast gene expression

1985 ◽  
Vol 5 (7) ◽  
pp. 1543-1553
Author(s):  
G S Roeder ◽  
C Beard ◽  
M Smith ◽  
S Keranen
Keyword(s):  
Gene Product ◽  
Regulatory Region ◽  
Negative Regulator ◽  
Transcriptional Level ◽  
Wild Type ◽  
Isolation And Characterization ◽  
Mutant Strains ◽  
Insertion Mutations ◽  
His4 Gene

The his4-917 mutation of Saccharomyces cerevisiae results from the insertion of the Ty element Ty917 into the regulatory region of the HIS4 gene and renders the cell His-. The hist4-912 delta mutant, which carries a solo delta in the 5'-noncoding region of HIS4, is His+ at 37 degrees C but His- at 23 degrees C. Both these mutations interfere with HIS4 expression at the transcriptional level. The His- phenotype of both insertion mutations is suppressed by mutations at the SPT2 locus. The product of the wild-type SPT2 gene apparently represses HIS4 transcription in these mutant strains; this repression is relieved when the SPT2 gene is destroyed by mutation. The repression of transcription by SPT2 presumably results from an interaction between the SPT2+ gene product and Ty or delta sequences. In this paper, we report the cloning and DNA sequence analysis of the wild-type SPT2 gene and show that the gene is capable of encoding a protein of 333 amino acids in length. In addition, we show that a dominant mutation of the SPT2 gene results from the generation of an ochre codon which is presumed to lead to a shortened SPT2 gene product.

Reirradiation for inoperable in-field recurrences of malignant gliomas

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 12527-12527
Author(s):  
U. Schäfer
Keyword(s):  
Malignant Gliomas ◽  
Treatment Protocol ◽  
Event Free Survival ◽  
Clinical Progression ◽  
Free Survival ◽  
Kaplan Meier ◽  
Acute Side Effects ◽  
Standardized Treatment ◽  
Late Treatment ◽  
Sequential Radiochemotherapy

12527 Background: To evaluate the effect of sequential radiochemotherapy in preirradiated malignant gliomas in a phase II study. Methods: Sixteen patients (median age 61 years) were treated according to a standardized treatment protocol consisting of sequential radiochemotherapy. The chemotherapy (temozolomide) was carried out over a duration of 5 consequential days (Mon-Fri) with a dose of 200 mg/m2/d. Chemotherapy courses were repeated in 4 week intervals (day 1, 29, 57, etc.) until clinical progression. Radiotherapy with 30 Gy over 3 weeks (5 x 2 Gy/week) was interposed between the first two chemotherapy courses (days 8–26). Results: 14/16 patients had no acute side effects. One patient suffered from acute thrombocytopenia (6000x106/l) and leukocytopenia (0,6x106/l), a further patient developed mental degradation (treatment stopped at 24 Gy). All patients have died due to disease progression. Median event-free survival (Kaplan/Meier method) amounts to 6 months. 7/16 patients survived longer than 10 months and one patient longer than 2 years. Late treatment sequelae have not been observed so far. Conclusions: The reported radiochemotherapy protocol is feasible for these otherwise difficult to treat patients without a remarkable increase in toxicity. In individual cases it can lead to stable disease over a period of 10 months and more. No significant financial relationships to disclose.

scholarly journals LncRNA MSC-AS1 Is a Diagnostic Biomarker and Predicts Poor Prognosis in Patients With Gastric Cancer by Integrated Bioinformatics Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Wei Yang ◽  
Fusheng Ge ◽  
Shuaibing Lu ◽  
Zhiming Shan ◽  
Liangqun Peng ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Logistic Regression ◽  
Survival Analysis ◽  
Mapk Pathway ◽  
Gene Set Enrichment Analysis ◽  
Wild Type ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
The Impact

Numerous studies have shown that long uncoded RNA (lncRNA) MSC-AS1 may play an important role in the occurrence and development of some types of cancer. However, its role in gastric cancer has rarely been discussed. This study aimed to clarify the association between lncRNA MSC-AS1 and gastric cancer using The Cancer Genome Atlas (TCGA) database. We determined the expression of MSC-AS1 using the Wilcoxon rank sum test; in addition, logistic regression was applied to evaluate the association between MSC-AS1 and clinicopathological characteristics. Also, Kaplan-Meier and Cox regression were used to evaluate the relationship between MSC-AS1 and survival. A nomogram was conducted to predict the impact of MSC-AS1 on prognosis. Moreover, Gene Set enrichment analysis (GSEA) was performed to annotate the biological function of MSC-AS1. Quantitative analysis of immune infiltration was carried out by single-set GSEA (ssGSEA). The MSC-AS1 level was elevated in gastric cancer tissues. An increased MSC-AS1 level was significantly correlated with T stage (odds ratio [OR] = 2.55 for T3 and T4 vs. T1 and T2), histological type (OR = 5.28 for diffuse type vs. tubular type), histological grade (OR = 3.09 for grade 3 vs. grades 1 and 2), TP53 status (OR = 0.55 for mutated vs. wild type), and PIK3CA status (OR = 0.55 for mutated vs. wild type) (all p &lt; 0.05) by univariate logistic regression. Kaplan-Meier survival analysis showed high MSC-AS1 expression had a poor overall survival [hazard ratio (HR) = 1.75; 95% confidence interval (CI): 1.25–2.45; p = 0.001] and progression-free interval (HR = 1.47; 95% CI: 1.03–2.10; p = 0.034). Multivariate survival analysis revealed that MSC-AS1 expression (HR = 1.681; 95% CI: 1.057–2.673; p = 0.028) was independently correlated with overall survival. GSEA demonstrated that the P38/MAPK pathway, the VEGF pathway, the cell adhesion molecules cams, the NOD-like receptor signaling pathway were differentially enriched in the high MSC-AS1 expression phenotype. SsGSEA and Spearman correlation revealed the relationships between MSC-AS1 and macrophages, NK cells, and Tems were the strongest. Coregulatory proteins were included in the PPI network. Upregulated lncRNA MSC-AS1 might be a potential biomarker for the diagnosis and prognosis of gastric cancer.

Immune mediated destruction of platelets in dogs with heat stroke: A prospective study

2009 ◽  
Vol 37 (05) ◽  
pp. 314-318 ◽  
Author(s):  
L. Keller ◽  
K. Meichner ◽  
S. Unterer ◽  
K. Hartmann ◽  
I. Zenker
Keyword(s):  
Heat Stroke ◽  
Treatment Protocol ◽  
Severe Thrombocytopenia ◽  
Prospective Evaluation ◽  
Antiplatelet Antibodies ◽  
Time Period ◽  
Immune Mediated ◽  
Standardized Treatment ◽  
A Prospective Study ◽  
Risk For Bleeding

Summary Objective: Severe thrombocytopenia is a common sequelae to heat stroke in dogs. So far it has been hypothezised that it is due to disseminated intravascular coagulation. We hypothezised that it is due to immune mediated destruction via antiplatelet antibodies. Material and methods: Prospective evaluation of dogs with heat stroke from May 2005 to August 2008. Dogs that developed severe thrombocytopenia within 5 days of admission were included in the study. All dogs were treated with a standardized treatment protocol. In addition, they received either immunoglobulins or prednisolone. Results: Six dogs were presented with heat stroke during that time period. Four developed a severe thrombocytopenia. All four dogs tested positive for antiplatelet antibodies and did not have elevated D-Dimers at that time. Platelet count in three dogs recovered fully, one dog was euthanized due to liver and renal failure. Conclusion: In those cases thrombocytopenia was due to immune mediated destruction not due to DIC. Clinical rele-vance: Due to the severity of the thrombocytopenia and the high risk for bleeding in those patients, immunosuppressive therapy in addition to DIC prophylaxis should be discussed.

Functional characterization of the H+/K+ ATPase in wild type and gastrin knock-out mice

2007 ◽  
Vol 45 (05) ◽  
Author(s):  
A Schnur ◽  
P Hegyi ◽  
V Venglovecz ◽  
Z Rakonczay ◽  
I Ignáth ◽  
...  
Keyword(s):  
Functional Characterization ◽  
Wild Type ◽  
Knock Out ◽  
Knock Out Mice

Characterization of Ischemic Stroke in CT Images using Image Processing

2017 ◽  
Vol 7 (9) ◽  
pp. 18
Author(s):  
Amal Alzain ◽  
Suhaib Alameen ◽  
Rani Elmaki ◽  
Mohamed E. M. Gar-Elnabi
Keyword(s):  
Ischemic Stroke ◽  
White Matter ◽  
Classification Accuracy ◽  
Ct Images ◽  
Gray Level ◽  
Level Variation ◽  
Interactive Data ◽  
The Brain ◽  
Brain Tissues

This study concern to characterize the brain tissues to ischemic stroke, gray matter, white matter and CSF using texture analysisto extract classification features from CT images. The First Order Statistic techniques included sevenfeatures. To find the gray level variation in CT images it complements the FOS features extracted from CT images withgray level in pixels and estimate the variation of thesubpatterns. analyzing the image with Interactive Data Language IDL software to measure the grey level of images. The results show that the Gray Level variation and   features give classification accuracy of ischemic stroke 97.6%, gray matter95.2%, white matter 97.3% and the CSF classification accuracy 98.0%. The overall classification accuracy of brain tissues 97.0%.These relationships are stored in a Texture Dictionary that can be later used to automatically annotate new CT images with the appropriate brain tissues names.

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