A Combination of Radiosurgery and Soluble Tissue Factor Enhances Vascular Targeting for Experimental Glioblastoma

Radiosurgery for glioblastoma is limited to the development of resistance, allowing tumor cells to survive and initiate tumor recurrence. Based on our previous work that coadministration of tissue factor and lipopolysaccharide following radiosurgery selectively induced thrombosis in cerebral arteriovenous malformations, achieving thrombosis of 69% of the capillaries and 39% of medium sized vessels, we hypothesized that a rapid and selective shutdown of the capillaries in glioblastoma vasculature would decrease the delivery of oxygen and nutrients, reducing tumor growth, preventing intracranial hypertension, and improving life expectancy. Glioblastoma was formed by implantation of GL261 cells into C57Bl/6 mouse brain. Mice were intravenously injected tissue factor, lipopolysaccharide, a combination of both, or placebo 24 hours after radiosurgery. Control mice received both agents after sham irradiation. Coadministration of tissue factor and lipopolysaccharide led to the formation of thrombi in up to 87 ± 8% of the capillaries and 46 ± 4% of medium sized vessels within glioblastoma. The survival rate of mice in this group was 80% versus no survivor in placebo controls 30 days after irradiation. Animal body weight increased with time in this group (r=0.88,P=0.0001). Thus, radiosurgery enhanced treatment with tissue factor, and lipopolysaccharide selectively induces thrombosis in glioblastoma vasculature, improving life expectancy.

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Endothelial Gene Expression and Molecular Changes in Response to Radiosurgery inIn VitroandIn VivoModels of Cerebral Arteriovenous Malformations

BioMed Research International ◽

10.1155/2013/408253 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Jian Tu ◽

Zhiqiang Hu ◽

Zhongbin Chen

Keyword(s):

Gene Expression ◽

Tissue Factor ◽

Arteriovenous Malformations ◽

Radiation Doses ◽

Dependent Manner ◽

Cerebral Arteriovenous Malformations ◽

Molecular Changes ◽

Time Points ◽

Endothelial Gene Expression ◽

Dose Dependent

Radiosurgery for cerebral arteriovenous malformations (AVMs) is limited to 2-year latency. There is no early marker to monitor whether the lesion is responsive to radiosurgery. In this study, we examined endothelial gene expression and molecular changes in response to radiosurgery. Gene expression of E- and P-selectin, ICAM-1, PECAM-1, VCAM-1, tissue factor, and vWF in human cerebral microvascular endothelial cells was quantified by RT-qPCR at different radiation doses and time points. Soluble E- and P-selectin, ICAM-1, VCAM-1, and tissue factor in an animal model of AVMs were quantified by ELISA at different time after radiosurgery. We found that gene expression of E- and P-selectin, ICAM-1, PECAM-1, and VCAM-1 was upregulated by radiation in a dose-dependent manner (P<.05). Gene expression of E- and P-selectin and ICAM-1 was more sensitive to irradiation than that of PECAM-1 and VCAM-1. Radiosurgery induced gene expression of P-selectin, ICAM-1, PECAM-1, and VCAM-1 was linearly correlated with time (P<.05). Radiosurgery induced elevation of soluble E- and P-selectin, ICAM-1, VCAM-1, and tissue factor in a rat model of AVMs (P<.05). Thus, a combination of these molecules measured at different time points may serve as an early predictor of responsiveness of AVMs to radiosurgery.

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The new paradigm of obesity

Problems of Endocrinology ◽

10.14341/probl201460543-48 ◽

2014 ◽

Vol 60 (5) ◽

pp. 43-48 ◽

Cited By ~ 1

Author(s):

I V Samorodskaya

Keyword(s):

Body Mass Index ◽

Body Weight ◽

Survival Rate ◽

Life Expectancy ◽

Chronic Diseases ◽

American Association ◽

Healthcare Providers ◽

The Body ◽

New Paradigm ◽

Elevated Body Mass Index

Despite the well-proved relationship between obesity and a number of chronic diseases, the information about the influence of the body weight on the life expectancy is contradictory. A wealth of literature publications deal with the paradoxical relation of the survival rate to obesity that manifests itself among the patients with the elevated body mass index (BMI) and moderate obesity as opposed to the patients having the normal or lowered BMI. The American Association of Endocrinologists proposed the new paradigm of the evaluation of BMI and obesity. The consensus of the Russian specialists as regards this paradigm needs to be reached in conjunction with the development of the relevant guidelines for practicing healthcare providers.

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Gamma knife radiosurgery for cerebral arteriovenous malformations in children/adolescents and adults. Part II: Differences in obliteration rates, treatment-obliteration intervals, and prognostic factors

Yearbook of Neurology and Neurosurgery ◽

10.1016/s0513-5117(08)70168-6 ◽

2007 ◽

Vol 2007 ◽

pp. 242

Author(s):

W.B. Gormley

Keyword(s):

Prognostic Factors ◽

Gamma Knife ◽

Arteriovenous Malformations ◽

Gamma Knife Radiosurgery ◽

Cerebral Arteriovenous Malformations ◽

Adolescents And Adults

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E-009 Initial experience of curative transvenous embolization of cerebral arteriovenous malformations using rapid ventricular pacing for flow arrest

10.1136/neurintsurg-2021-snis.105 ◽

2021 ◽

Author(s):

A White ◽

J Corona ◽

R Joshi ◽

B Welch

Keyword(s):

Arteriovenous Malformations ◽

Initial Experience ◽

Transvenous Embolization ◽

Ventricular Pacing ◽

Cerebral Arteriovenous Malformations ◽

Rapid Ventricular Pacing

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Endovascular Management of Cerebral Arteriovenous Malformations: Technical and Clinical Outcome

10.1055/s-0041-1729057 ◽

2020 ◽

Author(s):

Ahmed Attia Ahmed Hassan ◽

Ali Hassan Elmokadem ◽

Ahmed Bahaa Elden Elserwi ◽

Mohamed Metwally Abo El Atta ◽

Talal Ahmed Youssef Amer

Keyword(s):

Clinical Outcome ◽

Arteriovenous Malformations ◽

Endovascular Management ◽

Cerebral Arteriovenous Malformations

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Survival Analysis of Geriatric Patients with Low Digestive Hemorrhage Attending an Emergency Department

Gerontology ◽

10.1159/000513245 ◽

2021 ◽

pp. 1-6

Author(s):

Ana Fernandez-Suárez ◽

Oriol Yuguero Torres

Keyword(s):

Emergency Department ◽

Survival Analysis ◽

Retrospective Study ◽

Survival Rate ◽

Life Expectancy ◽

Antiplatelet Therapy ◽

Geriatric Patients ◽

Digestive Hemorrhage ◽

Kaplan Meier ◽

Number Of Individuals

Background: The increase in life expectancy and low mortality have doubled the number of individuals older than 65 in the last 30 years. Methods: We conducted a retrospective study of 101 patients older than 80 years of age treated by low digestive hemorrhage (LDH) in an emergency department during 2018. Sociodemographic variables were evaluated, as well as comorbidity and survival at 18 months. Survival was assessed by a Kaplan-Meier test. Results: 52.5% of the subjects were women. The average comorbidity of the sample was 1.97. The survival rate per year was 60%. The finding on colonoscopy shows no association with mortality. However, those patients on anticoagulant/antiplatelet therapy have a higher survival rate. Conclusion: Survival per year is high, so urgent colonoscopy for an LDH should be performed after evaluating the patient’s stability and functional status in a scheduled and outpatient manner.

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