scholarly journals ATIM-14. FIRST KOREAN EXPERIENCE OF DENDRITE CELL-BASED IMMUNOTHERAPY IN PATIENTS WITH PRIMARY GLIOBLASTOMA

2016 ◽  
Vol 18 (suppl_6) ◽  
pp. vi20-vi21
Author(s):  
Jaejoon Lim ◽  
Kyung gi Cho
Keyword(s):  
Primary Glioblastoma ◽  
Dendrite Cell

scholarly journals Elevated levels of IL-1β in Fanconi anaemia group A patients due to a constitutively active phosphoinositide 3-kinase-Akt pathway are capable of promoting tumour cell proliferation

2009 ◽  
Vol 422 (1) ◽  
pp. 161-170 ◽  
Author(s):  
Ana Ibáñez ◽  
Paula Río ◽  
José Antonio Casado ◽  
Juan Antonio Bueren ◽  
José Luis Fernández-Luna ◽  
...  
Keyword(s):  
Glycogen Synthase ◽  
Bone Marrow Failure ◽  
Nuclear Factor Κb ◽  
Hereditary Disease ◽  
Akt Pathway ◽  
Fanconi Anaemia ◽  
Primary Glioblastoma ◽  
A Cells ◽  
Group A ◽  
Phosphoinositide 3 Kinase

FA (Fanconi anaemia) is a hereditary disease characterized by congenital malformations, progressive bone marrow failure and an extraordinary elevated predisposition to develop cancer. In the present manuscript we describe an anomalous high level of the proinflammatory cytokine IL-1β (interleukin-1β) present in the serum of FA patients. The elevated levels of IL-1β were completely reverted by transduction of a wild-type copy of the FancA cDNA into FA-A (FA group A) lymphocytes. Although the transcription factor NF-κB (nuclear factor-κB) is a well established regulator of IL-1β expression, our experiments did not show any proof of elevated NF-κB activity in FA-A cells. However, we found that the overexpression of IL-1β in FA-A cells is related to a constitutively activated PI3K (phosphoinositide 3-kinase)-Akt pathway in these cells. We provide evidence that the effect of Akt on IL-1β activation is mediated by the inhibition of GSK3β (glycogen synthase kinase 3β). Finally, our data indicate that the levels of IL-1β produced by FA-A lymphoblasts are enough to promote an activation of the cell cycle in primary glioblastoma progenitor cells. Together, these results demonstrate that the constitutive activation of the PI3K-Akt pathway in FA cells upregulates the expression of IL-1β through an NF-κB-independent mechanism and that this overproduction activates the proliferation of tumour cells.

scholarly journals Homozygous MTAP deletion in primary human glioblastoma is not associated with elevation of methylthioadenosine

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yasaman Barekatain ◽  
Jeffrey J. Ackroyd ◽  
Victoria C. Yan ◽  
Sunada Khadka ◽  
Lin Wang ◽  
...  
Keyword(s):  
Clinical Relevance ◽  
Homozygous Deletion ◽  
In Vitro Models ◽  
Arginine Methyltransferase ◽  
Human Glioblastoma ◽  
Primary Glioblastoma ◽  
Methylthioadenosine Phosphorylase ◽  
Metabolomic Profiling

AbstractHomozygous deletion of methylthioadenosine phosphorylase (MTAP) in cancers such as glioblastoma represents a potentially targetable vulnerability. Homozygous MTAP-deleted cell lines in culture show elevation of MTAP’s substrate metabolite, methylthioadenosine (MTA). High levels of MTA inhibit protein arginine methyltransferase 5 (PRMT5), which sensitizes MTAP-deleted cells to PRMT5 and methionine adenosyltransferase 2A (MAT2A) inhibition. While this concept has been extensively corroborated in vitro, the clinical relevance relies on exhibiting significant MTA accumulation in human glioblastoma. In this work, using comprehensive metabolomic profiling, we show that MTA secreted by MTAP-deleted cells in vitro results in high levels of extracellular MTA. We further demonstrate that homozygous MTAP-deleted primary glioblastoma tumors do not significantly accumulate MTA in vivo due to metabolism of MTA by MTAP-expressing stroma. These findings highlight metabolic discrepancies between in vitro models and primary human tumors that must be considered when developing strategies for precision therapies targeting glioblastoma with homozygous MTAP deletion.

scholarly journals INNV-17. NEXT GENERATION SEQUENCING IMPACTS OUTCOMES IN RECURRENT PRIMARY GLIOBLASTOMA: A SINGLE-CENTER RETROSPECTIVE ANALYSIS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii120-ii120
Author(s):  
Daniel Zeitouni ◽  
Michael Catalino ◽  
Jordan Wise ◽  
Kathryn Pietrosimone ◽  
Sean McCabe ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Cox Model ◽  
Objective Response ◽  
Complete Response ◽  
High Rate ◽  
Next Generation ◽  
Disease Response ◽  
Primary Glioblastoma ◽  
Generation Sequencing ◽  
Recurrent Gbm

Abstract BACKGROUND GBM is driven by various genomic alterations. Next generation sequencing (NGS) may reveal targetable alterations. The goal of this study was to describe how NGS can inform targeted therapy (TT) selection. METHODS The medical records of patients (pts) with GBM from 2017–2019 were reviewed. Pts with actionable mutations were included in the analysis. At first progression (PD1), two cohorts of pts were defined: cohort A received TT, while cohort B received physician’s choice chemotherapy (PCC). Regression analyses were used to determine OS and PFS between cohorts. A stratified cox model was utilized to assess the effect of TT, where KPS level (low vs high) was utilized as a stratification factor. A heat map was generated describing the landscape of mutations. Disease response in cohort A was graded per RANO criteria. RESULTS There were 38 GBM pts with actionable alterations. Cohort A had 15 (39%) pts and cohort B had 23 (61%) pts. Of the 26 common alterations, 11 (42%) were deemed actionable. Pts with higher KPS were more likely to receive TT. Pts with a KPS ≥ 70 had a longer PFS while on TT. Although not well powered, pts in cohort A had a longer median OS relative to cohort B (HR 0.37 CI 0.10–1.38). The objective response rate (ORR) was 93%, with afatinib and cabozantinib resulting in complete response, one pt had progressive disease while on TT. CONCLUSION NGS for recurrent GBM yields a high rate of actionable alterations. Pts that go on TT are often younger and with higher KPS. This likely plays into their improved survival; however, it is notable that the high ORR reflects the value of NGS in deciding on TT to match alterations that are likely to respond. In conclusion, patient selection and availability of NGS impacts outcomes in recurrent GBM.

Primary Glioblastoma of Cerebellopontine Angle in Adult Mimicking Acoustic Neuroma

2019 ◽  
Vol 122 ◽  
pp. 48-52 ◽  
Author(s):  
Dian-xu Yang ◽  
Yao Jing ◽  
Zhi-ming Xu ◽  
Fang Yuan ◽  
Ying-liang Liu ◽  
...  
Keyword(s):  
Acoustic Neuroma ◽  
Cerebellopontine Angle ◽  
Primary Glioblastoma

scholarly journals Betulinic Acid-Mediated Tuning of PERK/CHOP Signaling by Sp1 Inhibition as a Novel Therapeutic Strategy for Glioblastoma

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 981 ◽  
Author(s):  
Wei-Lun Lo ◽  
Tsung-I Hsu ◽  
Wen-Bin Yang ◽  
Tzu-Jen Kao ◽  
Ming-Hsiao Wu ◽  
...  
Keyword(s):  
Betulinic Acid ◽  
Therapeutic Strategy ◽  
Cancer Therapies ◽  
Expression Array ◽  
Antitumor Effects ◽  
Apoptotic Pathway ◽  
Primary Glioblastoma ◽  
Signaling Activation ◽  
The Unfolded Protein Response ◽  
Resistant Cells

Patients with glioblastoma are at high risk of local recurrences after initial treatment with standard therapy, and recurrent tumor cells appear to be resistant to first-line drug temozolomide. Thus, finding an effective second-line agent for treating primary and recurrent glioblastomas is critical. Betulinic acid (BA), a natural product of plant origin, can cross the blood–brain barrier. Here, we investigated the antitumor effects of BA on typical glioblastoma cell lines and primary glioblastoma cells from patients, as well as corresponding temozolomide-resistant cells. Our findings verified that BA significantly reduced growth in all examined cells. Furthermore, gene-expression array analysis showed that the unfolded-protein response was significantly affected by BA. Moreover, BA treatment increased activation of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)/C/EBP homologous protein (CHOP) apoptotic pathway, and reduced specificity protein 1 (Sp1) expression. However, Sp1 overexpression reversed the observed cell-growth inhibition and PERK/CHOP signaling activation induced by BA. Because temozolomide-resistant cells exhibited significantly increased Sp1 expression, we concluded that Sp1-mediated PERK/CHOP signaling inhibition protects glioblastoma against cancer therapies; hence, BA treatment targeting this pathway can be considered as an effective therapeutic strategy to overcome such chemoresistance and tumor relapse.

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