Expression of Adhesion Factors and Degrading Proteins in Primary and Secondary Glioblastomas and Their Precursor Tumors

1998 ◽  
Vol 18 (5-6) ◽  
pp. 271-284 ◽  
Author(s):  
Dominique S. Tews ◽  
Anja Nissen
Keyword(s):  
Secondary Glioblastomas

scholarly journals Evaluating Mechanisms of IDH1 Regulation through Site-Specific Acetylation Mimics

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 740
Author(s):  
Joi Weeks ◽  
Alexandra I. Strom ◽  
Vinnie Widjaja ◽  
Sati Alexander ◽  
Dahra K. Pucher ◽  
...  
Keyword(s):  
Isocitrate Dehydrogenase ◽  
Translational Regulation ◽  
Catalytic Efficiency ◽  
Low Grade ◽  
Lysine Acetylation ◽  
Site Specific ◽  
Idh1 Mutations ◽  
Mutant Idh1 ◽  
Biochemical Features ◽  
Secondary Glioblastomas

Isocitrate dehydrogenase (IDH1) catalyzes the reversible NADP+-dependent oxidation of isocitrate to α-ketoglutarate (αKG). IDH1 mutations, primarily R132H, drive > 80% of low-grade gliomas and secondary glioblastomas and facilitate the NADPH-dependent reduction of αKG to the oncometabolite D-2-hydroxyglutarate (D2HG). While the biochemical features of human WT and mutant IDH1 catalysis have been well-established, considerably less is known about mechanisms of regulation. Proteomics studies have identified lysine acetylation in WT IDH1, indicating post-translational regulation. Here, we generated lysine to glutamine acetylation mimic mutants in IDH1 to evaluate the effects on activity. We show that mimicking lysine acetylation decreased the catalytic efficiency of WT IDH1, with less severe catalytic consequences for R132H IDH1.

scholarly journals Stability of the CpG island methylator phenotype during glioma progression and identification of methylated loci in secondary glioblastomas

BMC Cancer ◽  
2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Victoria K Hill ◽  
Thoraia Shinawi ◽  
Christopher J Ricketts ◽  
Dietmar Krex ◽  
Gabriele Schackert ◽  
...  
Keyword(s):  
Cpg Island ◽  
Cpg Island Methylator Phenotype ◽  
Methylator Phenotype ◽  
Secondary Glioblastomas ◽  
Glioma Progression

Frequent HRK inactivation associated with low apoptotic index in secondary glioblastomas

2005 ◽  
Vol 110 (4) ◽  
pp. 402-410 ◽  
Author(s):  
Mitsutoshi Nakamura ◽  
Eiwa Ishida ◽  
Keiji Shimada ◽  
Hiroyuki Nakase ◽  
Toshisuke Sakaki ◽  
...  
Keyword(s):  
Apoptotic Index ◽  
Secondary Glioblastomas

scholarly journals Frequent LOH on 22q12.3 and TIMP-3 inactivation occur in the progression to secondary glioblastomas

2004 ◽  
Vol 85 (2) ◽  
pp. 165-175 ◽  
Author(s):  
Mitsutoshi Nakamura ◽  
Eiwa Ishida ◽  
Keiji Shimada ◽  
Munehiro Kishi ◽  
Hiroyuki Nakase ◽  
...  
Keyword(s):  
Secondary Glioblastomas

PIK3CA alterations in primary (de novo) and secondary glioblastomas

2007 ◽  
Vol 113 (3) ◽  
pp. 295-302 ◽  
Author(s):  
Daisuke Kita ◽  
Yasuhiro Yonekawa ◽  
Michael Weller ◽  
Hiroko Ohgaki
Keyword(s):  
De Novo ◽  
Secondary Glioblastomas

Overexpression of the EGF Receptor and p53 Mutations are Mutually Exclusive in the Evolution of Primary and Secondary Glioblastomas

1996 ◽  
Vol 6 (3) ◽  
pp. 217-223 ◽  
Author(s):  
Kunihiko Watanabe ◽  
Osamu Tachibana ◽  
Kazufumi Sato ◽  
Yasuhiro Yonekawa ◽  
Paul Kleihues ◽  
...  
Keyword(s):  
Egf Receptor ◽  
P53 Mutations ◽  
Secondary Glioblastomas

scholarly journals ACTR-51. REMARKABLE RESPONSE OF A PATIENT WITH SECONDARY GBM TO A HISTONE DEACETYLASE INHIBITOR

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi25-vi25
Author(s):  
Hui-Kuo Shu ◽  
Saumya Gurbani ◽  
Karthik Ramesh ◽  
Brent Weinberg ◽  
Alfredo Voloschin ◽  
...  
Keyword(s):  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitors ◽  
Competitive Inhibition ◽  
Epigenetic Modification ◽  
Histone Deacetylation ◽  
Resonance Spectroscopy ◽  
Lower Grade ◽  
Primary Tumors ◽  
Secondary Glioblastoma ◽  
Secondary Glioblastomas

Abstract Glioblastomas are highly aggressive, grade IV tumors of glial cells that arise either as de novo primary tumors or as secondary tumors, which malignantly transformed from lower grade gliomas. Secondary glioblastomas have a relatively low incidence making up 5–10% of all glioblastoma diagnoses and tend to occur in younger patients. However, these tumors are still quite aggressive with survival outcomes that do not differ substantially from primary glioblastomas. Secondary glioblastomas also often harbor mutation of isocitrate dehydrogenase (IDH) enzyme, which produces the oncometabolite 2-hydroxyglutarate (2-HG) from alpha-ketoglutarate (α-KG). The accumulation of 2-HG has several downstream effects due to its competitive inhibition of α-KG-dependent enzymes, including epigenetic modification via hypermethylation of histones. Histone deacetylase inhibitors (HDACi) are a class of molecules that inhibit histone deacetylation and have been shown to have anti-tumor effect in part due to this epigenetic modification. Thus, because of their shared targets with regard to histone modification, it is plausible that HDACi could counter the oncometabolite effects of accumulated 2-HG in IDH1 mutant tumors. Since belinostat is a pan-HDACi that has improved blood-brain barrier penetration compared to many other HDACis, we conducted a pilot study that enrolled 15 patients examining its upfront use for the treatment of glioblastomas and found that it was well tolerated. One patient in particular, likely with secondary glioblastoma harboring the typical IDH1 mutation, underwent treatment with standard chemoradiation as well as belinostat on this study. For this case, a remarkable improvement in tumor burden with very significant decrease in enhancing residual tumor and restoration of magnetic resonance spectroscopy (MRS)-detectable metabolism was noted. Furthermore, improved neurocognitition and quality-of-life were also observed in this patient during the 18-month follow-up period. Collectively, these outcomes potentially support the use of belinostat as an adjuvant therapy for patients with secondary glioblastoma that harbor a mutant IDH enzyme.

The value of promoter methylation of the MGMT gene and IDH mutations in secondary glioblastomas.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22193-e22193
Author(s):  
Li Bie ◽  
Qian Yun Li
Keyword(s):  
Promoter Methylation ◽  
Median Survival Time ◽  
Idh1 Mutation ◽  
Idh Mutation ◽  
Mgmt Methylation ◽  
Mgmt Gene ◽  
Idh Mutations ◽  
Group 2 ◽  
Improved Outcome ◽  
Secondary Glioblastomas

e22193 Background: Several studies have observed a change in MGMT silencing and IDH1 mutation in secondary glioblastomas (sGBMs). However, reports about the prognostic value of promoter methylation of the MGMT gene and IDH mutations in secondary glioblastomas (sGBMs) are few in number. Methods: The study involved primary and secondary tumor tissue samples from 89 GBMs pts (P/S: 42/47) diagnosed and treated within the First Hospital of Jilin University from Jan 2006 to Nov 2011. After surgical treatment, all GBM pts were subjected to radiotherapy with concomitant administration of TMZ. Pts with GBM were screened for promoter status of MGMT gene, by the methylation-specific polymerase chain reaction (MSP), and, for IDH mutations by direct sequencing. Results: A total of 42 of 89 pts (47.2%) had primary GBMs (pGBMs) (Group 1), while 47 pts (52.8%) had secondary GBMs (Group 2). In Group 2, 23 pts (21/47, 44.7%) developed a sGBM through progression from a low grade glioma (LGG) WHO grade II and a secondary anaplastic gliomas (sAG) (Group 2a), whereas 26 pts (26/47, 55.3%) showed a direct malignant transformation from a LGG to a sGBM (Group 2b). MGMT methylation was observed in 38 (42.7%) GBMs, with a higher frequency in sGBMs than pGBMs (24/14, 51.1 vs. 33.3%; p = 0.008). MGMT methylation status was associated with increased median survival time in pGBMs and sGBMs pts. IDH1 mutations are present in the majority of sGBMs but rare in pGBMs (31/5, 66.0 vs. 11.9%; p < 0.001). Group 2a had a higher frequency with IDH1 mutation than group 2b (18/12, 78.3 vs. 46.2%; p < 0.01). The median survival time after malignant progression of all sGBMs pts with an IDH mutation was longer than in pts with wild-type IDH (3.2 vs. 1.1ys; p < 0.01). IDH1 mutation had an improved outcome in group2a, which is compared with group 2b (3.9 ys vs. 2.1 ys; p < 0.05). Conclusions: In our population, pts with sGBM and IDH mutation had a significantly improved outcome. In addition, MGMT methylation is also a powerful prognostic marker in sGBM pts.

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