scholarly journals Sox7 promotes high-grade glioma by increasing VEGFR2-mediated vascular abnormality

2018 ◽  
Vol 215 (3) ◽  
pp. 963-983 ◽  
Author(s):  
Il-Kug Kim ◽  
Kangsan Kim ◽  
Eunhyeong Lee ◽  
Dong Sun Oh ◽  
Chan Soon Park ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Vascular Function ◽  
Antiangiogenic Therapy ◽  
High Grade Glioma ◽  
Early Recurrence ◽  
High Grade ◽  
Poor Survival ◽  
Antibody Treatment ◽  
Vascular Abnormality ◽  
T Cell Infiltration

High-grade glioma (HGG) is highly angiogenic, but antiangiogenic therapy has transient clinical benefit in only a fraction of patients. Vascular regulators of these heterogeneous responses remain undetermined. We found up-regulation of Sox7 and down-regulation of Sox17 in tumor endothelial cells (tECs) in mouse HGG. Sox7 deletion suppressed VEGFR2 expression, vascular abnormality, hypoxia-driven invasion, regulatory T cell infiltration, and tumor growth. Conversely, Sox17 deletion exacerbated these phenotypes by up-regulating Sox7 in tECs. Anti-VEGFR2 antibody treatment delayed tumor growth by normalizing Sox17-deficient abnormal vessels with high Sox7 levels but promoted it by regressing Sox7-deficient vessels, recapitulating variable therapeutic responses to antiangiogenic therapy in HGG patients. Our findings establish that Sox7 promotes tumor growth via vessel abnormalization, and its level determines the therapeutic outcome of VEGFR2 inhibition in HGG. In 189 HGG patients, Sox7 expression was heterogeneous in tumor vessels, and high Sox7 levels correlated with poor survival, early recurrence, and impaired vascular function, emphasizing the clinical relevance of Sox7 in HGG.

Urotensin II receptor endogenous ligands as new candidates involved in high grade glioma tumor growth and neo-angiogenesis

2012 ◽  
Vol 177 ◽  
pp. S26
Author(s):  
V. Le Joncour ◽  
C. Lecointre ◽  
M. Jarry ◽  
J.E. Joubert ◽  
M.T. Schouft ◽  
...  
Keyword(s):  
Tumor Growth ◽  
High Grade Glioma ◽  
High Grade ◽  
Urotensin Ii ◽  
Endogenous Ligands ◽  
Glioma Tumor

Change in Pattern of Relapse After Antiangiogenic Therapy in High-Grade Glioma

2012 ◽  
Vol 82 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Ashwatha Narayana ◽  
Saroj D. Kunnakkat ◽  
Praveen Medabalmi ◽  
John Golfinos ◽  
Erik Parker ◽  
...  
Keyword(s):  
Antiangiogenic Therapy ◽  
High Grade Glioma ◽  
High Grade

Antiangiogenic therapy using bevacizumab in recurrent high-grade glioma: impact on local control and patient survival

2009 ◽  
Vol 110 (1) ◽  
pp. 173-180 ◽  
Author(s):  
Ashwatha Narayana ◽  
Patrick Kelly ◽  
John Golfinos ◽  
Erik Parker ◽  
Glyn Johnson ◽  
...  
Keyword(s):  
Patient Survival ◽  
Chemotherapeutic Agent ◽  
Antiangiogenic Therapy ◽  
Progression Free Survival ◽  
High Grade Glioma ◽  
Median Number ◽  
Antiangiogenic Agents ◽  
High Grade ◽  
Diffuse Disease ◽  
High Grade Gliomas

Object Antiangiogenic agents have recently shown impressive radiological responses in high-grade glioma. However, it is not clear if the responses are related to vascular changes or due to antitumoral effects. The authors report the mature results of a clinical study of bevacizumab-based treatment of recurrent high-grade gliomas. Methods Sixty-one patients with recurrent high-grade gliomas received treatment with bevacizumab at 10 mg/ kg every 2 weeks for 4 doses in an 8-week cycle along with either irinotecan or carboplatin. The choice of concomitant chemotherapeutic agent was based on the number of recurrences and prior chemotherapy. Results At a median follow-up of 7.5 months (range 1–19 months), 50 (82%) of 61 patients relapsed and 42 patients (70%) died of the disease. The median number of administered bevacizumab cycles was 2 (range 1–7 cycles). The median progression-free survival (PFS) and overall survival (OS) were 5 (95% confidence interval [CI] 2.3–7.7) and 9 (95% CI 7.6–10.4) months, respectively, as calculated from the initiation of the bevacizumab-based therapy. Radiologically demonstrated responses following therapy were noted in 73.6% of cases. Neither the choice of chemotherapeutic agent nor the performance of a resection prior to therapy had an impact on patient survival. Although the predominant pattern of relapse was local, 15 patients (30%) had diffuse disease. Conclusions Antiangiogenic therapy using bevacizumab appears to improve survival in patients with recurrent high-grade glioma. A possible change in the invasiveness of the tumor following therapy is worrisome and must be closely monitored.

scholarly journals Intermittent radiotherapy as alternative treatment for recurrent high grade glioma: a modeling study based on longitudinal tumor measurements

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sarah C. Brüningk ◽  
Jeffrey Peacock ◽  
Christopher J. Whelan ◽  
Renee Brady-Nicholls ◽  
Hsiang-Hsuan M. Yu ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Treatment Option ◽  
Radiation Treatment ◽  
Phase 1 ◽  
High Grade Glioma ◽  
Patient Specific ◽  
Tumor Control ◽  
Model Parameters ◽  
High Dose ◽  
High Grade

AbstractRecurrent high grade glioma patients face a poor prognosis for which no curative treatment option currently exists. In contrast to prescribing high dose hypofractionated stereotactic radiotherapy (HFSRT, $$\ge 6$$ ≥ 6 Gy $$\times$$ × 5 in daily fractions) with debulking intent, we suggest a personalized treatment strategy to improve tumor control by delivering high dose intermittent radiation treatment (iRT, $$\ge 6$$ ≥ 6 Gy $$\times$$ × 1 every 6 weeks). We performed a simulation analysis to compare HFSRT, iRT and iRT plus boost ($$\ge 6$$ ≥ 6 Gy $$\times$$ × 3 in daily fractions at time of progression) based on a mathematical model of tumor growth, radiation response and patient-specific evolution of resistance to additional treatments (pembrolizumab and bevacizumab). Model parameters were fitted from tumor growth curves of 16 patients enrolled in the phase 1 NCT02313272 trial that combined HFSRT with bevacizumab and pembrolizumab. Then, iRT +/− boost treatments were simulated and compared to HFSRT based on time to tumor regrowth. The modeling results demonstrated that iRT + boost(− boost) treatment was equal or superior to HFSRT in 15(11) out of 16 cases and that patients that remained responsive to pembrolizumab and bevacizumab would benefit most from iRT. Time to progression could be prolonged through the application of additional, intermittently delivered fractions. iRT hence provides a promising treatment option for recurrent high grade glioma patients for prospective clinical evaluation.

scholarly journals Self-Renewal Does Not Predict Tumor Growth Potential in Mouse Models of High-Grade Glioma

Cancer Cell ◽  
2012 ◽  
Vol 21 (1) ◽  
pp. 11-24 ◽  
Author(s):  
Lindy E. Barrett ◽  
Zvi Granot ◽  
Courtney Coker ◽  
Antonio Iavarone ◽  
Dolores Hambardzumyan ◽  
...  
Keyword(s):  
Tumor Growth ◽  
Mouse Models ◽  
High Grade Glioma ◽  
Growth Potential ◽  
High Grade ◽  
Self Renewal

Antiangiogenic therapy for high-grade glioma

2014 ◽  
Author(s):  
Mustafa Khasraw ◽  
Malaka S Ameratunga ◽  
Robin Grant ◽  
Helen Wheeler ◽  
Nick Pavlakis
Keyword(s):  
Antiangiogenic Therapy ◽  
High Grade Glioma ◽  
High Grade

scholarly journals Development and Optimization of Irinotecan-Loaded PCL Nanoparticles and Their Cytotoxicity against Primary High-Grade Glioma Cells

Pharmaceutics ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 541
Author(s):  
Basant Salah Mahmoud ◽  
Christopher McConville
Keyword(s):  
Malignant Tumors ◽  
Double Emulsion ◽  
Glioma Cells ◽  
High Grade Glioma ◽  
Zero Order ◽  
High Grade ◽  
Spherical Nanoparticles ◽  
Poor Survival ◽  
Hydrophilic Drugs ◽  
Zero Order Release

Background: High-grade gliomas (HGGs) are highly malignant tumors with a poor survival rate. The inability of free drugs to cross the blood–brain barrier and their off-target accumulation result in dose-limiting side effects. This study aimed at enhancing the encapsulation efficiency (EE) of irinotecan hydrochloride trihydrate (IRH) within polycaprolactone (PCL) nanoparticles with optimized size and charge. Materials and Methods: IRH-loaded PCL nanoparticles were formulated using either the single emulsion (O/W, W/O and O/O) or double emulsion (W/O/O and W/O/W) solvent evaporation techniques. The nanoparticles were characterized for their size, zeta potential and EE, with the optimized nanoparticles being characterized for their drug release and cytotoxicity. Results: The amorphization of PCL and the addition of electrolytes to the aqueous phases of the W/O/W emulsion produced spherical nanoparticles with a mean diameter of 202.1 ± 2.0 nm and an EE of 65.0%. The IRH-loaded nanoparticles exhibited zero-order release and were cytotoxic against primary HGG cells. Conclusion: The amorphization of PCL improves its EE of hydrophilic drugs, while the addition of electrolytes to the aqueous phases of the W/O/W emulsion enhances their EE further. IRH-loaded PCL nanoparticles have the potential to deliver cytotoxic levels of IRH over a sustained period of time, enhancing the cell death of HGGs.

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