Publications by authors named "Andrew H Kaye"

144 Publications

Flow-diverter stents in the early management of acutely ruptured brain aneurysms: effective rebleeding protection with low thromboembolic complications.

J Neurosurg 2021 Apr 16:1-8. Epub 2021 Apr 16.

4Neurology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; and.

Objective: Flow-diverter stents (FDSs) are not generally used for the management of acutely ruptured aneurysms with associated subarachnoid hemorrhage (SAH). Herein, the authors present their experience with FDSs in this scenario, focusing on the antiplatelet regimen, perioperative management, and outcome.

Methods: The authors retrospectively reviewed their institutional database for the treatment and outcomes of all patients with acutely ruptured aneurysms and associated SAH from July 2010 to September 2018 who had received an FDS implant as stand-alone treatment within 4 days after diagnosis. The protocol with the use of flow diversion in these patients includes a low threshold for placement of external ventricular drains before stenting, followed by the administration of aspirin and clopidogrel with platelet testing before stent implantation. With this approach, the risk of hemorrhage and stent-related thrombus formation is limited. Demographic, clinical, technical, and imaging data were analyzed.

Results: Overall, 76 patients (61% females, mean age 42.8 ± 11.3 years) met the inclusion criteria. FDS implantation was performed a median of 2 days after diagnosis. On average, 1.05 devices were used per procedure. There was no procedural mortality directly attributed to the endovascular intervention. Procedural device-related clinical complications were recorded in a total of 6 cases (7.9%) and resulted in permanent neurological morbidity in 2 cases (2.6%). There was complete immediate aneurysm occlusion in 11 patients (14.5%), and persistent aneurysm filling was seen in 65 patients (85.5%). Despite this, no patient presented with rebleeding from the target aneurysm. There was an excellent clinical outcome in 62 patients (81.6%), who had a 90-day modified Rankin Scale score of 0-2. Among the 71 survivors, total or near-total occlusion was observed in 64/67 patients (95.5%) with a 3- to 6-month angiographic follow-up and in all cases evaluated at 12 months. Five patients (6.6%) died during follow-up for reasons unrelated to the procedure or new hemorrhage.

Conclusions: Flow diversion is an effective therapeutic strategy for the management of select acutely ruptured aneurysms. Despite low rates of immediate aneurysm occlusion after FDS implantation, the device exerts an important protective effect. The authors' experience confirmed no aneurysm rerupture, high rates of delayed complete occlusion, and complication rates that compare favorably with the rates obtained using other techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3171/2020.10.JNS201642DOI Listing
April 2021

Solid vs. cystic predominance in posterior fossa hemangioblastomas: implications for cerebrovascular risks and patient outcome.

Acta Neurochir (Wien) 2021 Apr 3. Epub 2021 Apr 3.

Department of Neurosurgery, Hadassah-Hebrew University Medical Center, P.O. Box 12000, 91120, Jerusalem, Israel.

Background: Hemangioblastomas (HGBs) are highly vascular benign tumors, commonly located in the posterior fossa, and 80% of them are sporadic. Patients usually present with features of raised intracranial pressure and cerebellar symptoms. HGB can be classified as either mostly cystic or solids. Although the solid component is highly vascularized, aneurysm or hemorrhagic presentation is rarely described, having catastrophic results.

Methods: We identified 32 consecutive patients with posterior fossa HBG who underwent surgery from 2008 through 2020 at our medical center. Tumors were classified as predominantly cystic or solid according to radiological features. Resection was defined as gross total (GTR) or subtotal (STR).

Results: During the study period, 32 posterior fossa HGBs were resected. There were 26 cerebellar lesions and 4 medullar lesions, and in 2 patients, both structures were affected. Predominant cystic tumors were seen in 15 patients and solids in 17. Preoperative digital subtraction angiography (DSA) was performed in 8 patients with solid tumors, and 4 showed tumor-related aneurysms. Embolization of the tumors was performed in 6 patients, including the four tumor-related aneurysms. GTR was achieved in 29 tumors (91%), and subtotal resection in 3 (9%). Three patients had postoperative lower cranial nerve palsy. Functional status was stable in 5 patients (16%), improved in 24 (75%), and 3 patients (9%) deteriorated. One patient died 2 months after the surgery. Two tumors recurred and underwent a second surgery achieving GTR. The mean follow-up was 42.7 months (SD ± 51.0 months).

Conclusions: Predominant cystic HGB is usually easily treated as the surgery is straightforward. Those with a solid predominance present a more complex challenge sharing features similar to arteriovenous malformations. Given the important vascular association of solid predominance HGB with these added risk factors, the preoperative assessment should include DSA, as in arteriovenous malformations, and endovascular intervention should be considered before surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00701-021-04828-wDOI Listing
April 2021

EGFRvIII Promotes Cell Survival during Endoplasmic Reticulum Stress through a Reticulocalbin 1-Dependent Mechanism.

Cancers (Basel) 2021 Mar 10;13(6). Epub 2021 Mar 10.

Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia.

Reticulocalbin 1 (RCN1) is an endoplasmic reticulum (ER)-residing protein, involved in promoting cell survival during pathophysiological conditions that lead to ER stress. However, the key upstream receptor tyrosine kinase that regulates RCN1 expression and its potential role in cell survival in the glioblastoma setting have not been determined. Here, we demonstrate that RCN1 expression significantly correlates with poor glioblastoma patient survival. We also demonstrate that glioblastoma cells with expression of EGFRvIII receptor also have high RCN1 expression. Over-expression of wildtype EGFR also correlated with high RCN1 expression, suggesting that EGFR and EGFRvIII regulate RCN1 expression. Importantly, cells that expressed EGFRvIII and subsequently showed high RCN1 expression displayed greater cell viability under ER stress compared to EGFRvIII negative glioblastoma cells. Consistently, we also demonstrated that RCN1 knockdown reduced cell viability and exogenous introduction of RCN1 enhanced cell viability following induction of ER stress. Mechanistically, we demonstrate that the EGFRvIII-RCN1-driven increase in cell survival is due to the inactivation of the ER stress markers ATF4 and ATF6, maintained expression of the anti-apoptotic protein Bcl-2 and reduced activity of caspase 3/7. Our current findings identify that EGFRvIII regulates RCN1 expression and that this novel association promotes cell survival in glioblastoma cells during ER stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers13061198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7999088PMC
March 2021

Temporal patterns of visual recovery following pituitary tumor resection: A prospective cohort study.

J Clin Neurosci 2021 Apr 16;86:252-259. Epub 2021 Feb 16.

Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand. Electronic address:

Significant restoration of visual function can occur following pituitary tumor resection, although the time course of visual recovery remains poorly understood. This single-centre, two-year, prospective cohort study investigated the temporal patterns of visual recovery in consecutive patients undergoing pituitary tumor resection, between 2009 and 2018. Eyes were stratified based on pre-operative optical coherence tomography (OCT) retinal nerve fibre layer (RNFL) thickness measurements, with thin RNFL being defined as those within the fifth-percentile of age-matched normative values, and normal RNFL as those above the fifth-percentile. Visual function and OCT parameters were assessed pre-operatively, and at 6 weeks, 6 months, and 2 years post-operatively. 456 eyes of 228 patients (mean ± SD age, 53 ± 15 years) were included, of which 114 (25%) eyes had thin RNFL pre-operatively. Visual field recovery was observed in both groups during the first 6 weeks post-operatively (all Q ≤ 0.02), although improvements in visual field parameters between 6 weeks to 6 months were limited to eyes with thin RNFL (both Q < 0.05). No further improvements in visual function were detected beyond 6 months in both groups (both Q > 0.50). Similar trends were observed in linear regression analysis according to baseline visual function in both groups. In summary, eyes with normal RNFL thickness at baseline experienced most of their recovery within the first six weeks following surgery, while eyes with thin RNFL exhibited gradual improvements during the first six months. These findings have important implications when providing patient counselling and prognostication in the pre-operative setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2021.01.007DOI Listing
April 2021

Acute visual deterioration and headaches in a patient with suprasellar lesion: Question.

J Clin Neurosci 2021 Apr 8;86:286-288. Epub 2021 Feb 8.

Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2021.01.040DOI Listing
April 2021

Acute visual deterioration and headaches in a patient with suprasellar lesion: Answer.

J Clin Neurosci 2021 Apr 7;86:312-314. Epub 2021 Feb 7.

Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2021.01.043DOI Listing
April 2021

Metastases to meningioma-review and meta-analysis.

Acta Neurochir (Wien) 2021 03 3;163(3):699-709. Epub 2021 Jan 3.

The Neurosurgery Department, Rambam (Maimonides) Medical Center, 2 Ha'aliya Street, 3109601, Haifa, Israel.

Purpose: Meningiomas are a common tumor within the cranial cavity. They may be a target for metastatic spread of cancer elsewhere in the body. We analyzed all the data in the literature about tumor-to-meningioma metastasis (TTMM).

Methods: We performed a meta-analysis using the PRISMA checklist to locate all cases of TTMM in the PubMed and Medline databases. We collected patient and cancer parameters, meningioma parameters, and clinical factors.

Results: We located 124 articles, describing 152 cases of patients with TTMM. The mean (± SD) age of all patients was 62.21 ± 10.8 years, with even distribution above and below the mean. Of the cases, 65.9% were reported in women. The most common cancer origins of TTMM were breast and lung carcinoma, followed by kidney, prostate, and GI tract carcinoma. Cancer status is not a good marker of TTMM when managing a meningioma. In 36.69% of cases, TTMM was the presentation of an unknown cancer. In nearly 60% of the known cases, cancer was considered in remission for at least 1 year. Meningioma parameters are unhelpful when considering a TTMM. The distribution of meningioma location is similar to other series of meningioma reported in the literature. Meningioma grade is similar to meningiomas without TTMM. In 57.89%, the patient presented with a focal deficit. Presenting factors were seizures, elevated ICP, and others. Over 95% of cases were symptomatic at presentation.

Conclusion: TTMM should be suspected in cases of meningioma in a patient with background cancer, regardless of meningioma parameters or cancer status.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00701-020-04661-7DOI Listing
March 2021

Cervical meningioma with resultant bifid appearing spinal cord.

J Clin Neurosci 2020 Nov 26;81:401-402. Epub 2020 Oct 26.

Department of Neurosurgery, Hadassah Hebrew University Hospital, Jerusalem, Israel.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2020.10.018DOI Listing
November 2020

Reduced EGFR and increased miR-221 is associated with increased resistance to temozolomide and radiotherapy in glioblastoma.

Sci Rep 2020 10 20;10(1):17768. Epub 2020 Oct 20.

Level 5, Clinical Sciences Building, Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC, 3050, Australia.

Despite aggressive treatment with temozolomide and radiotherapy and extensive research into alternative therapies there has been little improvement in Glioblastoma patient survival. Median survival time remains between 12 and 15 months mainly due to treatment resistance and tumor recurrence. In this study, we aimed to explore the underlying mechanisms behind treatment resistance and the lack of success with anti-EGFR therapy in the clinic. After generating a number of treatment resistant Glioblastoma cell lines we observed that resistant cell lines lacked EGFR activation and expression. Furthermore, cell viability assays showed resistant cells were significantly less sensitive to the anti-EGFR agents when compared to parental cell lines. To further characterise the resistance mechanism in our cells microRNA prediction software identified miR-221 as a negative regulator of EGFR expression. miR-221 was up-regulated in our resistant cell lines, and this up-regulation led to a significant reduction in EGFR expression in both our cultured cell lines and a large cohort of glioblastoma patient tumor tissue.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-74746-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7576591PMC
October 2020

Inhibition of Radiation and Temozolomide-Induced Glioblastoma Invadopodia Activity Using Ion Channel Drugs.

Cancers (Basel) 2020 Oct 8;12(10). Epub 2020 Oct 8.

Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville 3050, Victoria, Australia.

Glioblastoma (GBM) is the most prevalent and malignant type of primary brain cancer. The rapid invasion and dissemination of tumor cells into the surrounding normal brain is a major driver of tumor recurrence, and long-term survival of GBM patients is extremely rare. Actin-rich cell membrane protrusions known as invadopodia can facilitate the highly invasive properties of GBM cells. Ion channels have been proposed to contribute to a pro-invasive phenotype in cancer cells and may also be involved in the invadopodia activity of GBM cells. GBM cell cytotoxicity screening of several ion channel drugs identified three drugs with potent cell killing efficacy: flunarizine dihydrochloride, econazole nitrate, and quinine hydrochloride dihydrate. These drugs demonstrated a reduction in GBM cell invadopodia activity and matrix metalloproteinase-2 (MMP-2) secretion. Importantly, the treatment of GBM cells with these drugs led to a significant reduction in radiation/temozolomide-induced invadopodia activity. The dual cytotoxic and anti-invasive efficacy of these agents merits further research into targeting ion channels to reduce GBM malignancy, with a potential for future clinical translation in combination with the standard therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12102888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599723PMC
October 2020

Correction to: Serum microRNA is a biomarker for post-operative monitoring in glioma.

J Neurooncol 2020 Sep;149(3):401

Department of Surgery, University of Melbourne, Parkville, VIC, Australia.

For the reference citation '[57]' in the second paragraph of the Results section of the original article there was no corresponding entry in the References section. It should have referred to the below mentioned article by Ebrahimkhani et al. (2018).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-020-03630-5DOI Listing
September 2020

Serum microRNA is a biomarker for post-operative monitoring in glioma.

J Neurooncol 2020 Sep 11;149(3):391-400. Epub 2020 Sep 11.

Department of Surgery, University of Melbourne, Parkville, VIC, Australia.

Purpose: A circulating biomarker has potential to provide more accurate information for glioma progression post treatment, however no such biomarker is currently available. We aimed to discover a microRNA serum biomarker for longitudinal monitoring of glioma patients.

Methods: A prospectively collected cohort of 91 glioma patients and 17 healthy controls underwent pre and post-operative serum miRNA profiling using Nanostring®. Differentially expressed miRNAs were discovered using a machine learning random forest analysis. Candidate miRNAs were then assessed by droplet digital PCR in 11 patients with multiple follow up samples and compared to tumor volume based on magnetic resonance imaging.

Results: A 9-gene miRNA signature was identified that could distinguish between glioma and healthy controls with 99.8% accuracy. Two miRNAs miR-223 and miR-320e, best demonstrated dynamic changes that correlated closely with tumor volume in LGG and GBM respectively. Importantly, miRNA levels did not increase in two cases of pseudo-progression, indicating the potential utility of this test in guiding treatment decisions.

Conclusions: We identified a highly accurate 9-miRNA signature associated with glioma serum. Additionally, we observed dynamic changes in specific miRNAs correlating with tumor volume over long-term follow up. These results support a large prospective validation study of serum miRNA biomarkers in glioma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11060-020-03566-wDOI Listing
September 2020

Dural based tumor causing cognitive decline: Answer.

J Clin Neurosci 2020 Feb 20;72:493-494. Epub 2019 Nov 20.

Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.10.019DOI Listing
February 2020

Dural based tumor causing cognitive decline: Question.

J Clin Neurosci 2020 Feb 9;72:420. Epub 2019 Nov 9.

Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.10.016DOI Listing
February 2020

Progressive facial numbness in a patient with multiple enhancing dural based tumours: Answer.

J Clin Neurosci 2020 Aug;78:444-445

Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address:

Sarcoidosis is uncommon multiple organ granulomatous disease of unknown etiology. Neurosarcoidosis occurs in about 5% of cases and most frequently follows systemic disease. We present a case of 52-years-old woman with a progressive hemifacial paresthesia and multiple enhancing dural based lesions. Resection of the right frontal mass allowed for the diagnosis to be made. The patient had no other features of sarcoidosis. Therefore, the diagnosis of neurosarcoidosis, especially when unaccompanied by systemic features can be challenging but should be considered in the differential diagnosis of multiple enhancing dural based tumours.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2020.07.035DOI Listing
August 2020

Progressive facial numbness in a patient with multiple enhancing dural based tumours: Question.

J Clin Neurosci 2020 Aug 27;78:387-388. Epub 2020 Mar 27.

Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. Electronic address:

Sarcoidosis is uncommon multiple organ granulomatous disease of unknown etiology. Neurosarcoidosis occurs in about 5% of cases and most frequently follows systemic disease. We present a case of 52 -years -old woman with a progressive hemifacial paresthesia and multiple enhancing dural based lesions. Resection of the right frontal mass allowed for the diagnosis to be made. The patient had no other features of sarcoidosis. Therefore, the diagnosis of neurosarcoidosis, especially when unaccompanied by systemic features can be challenging but should be considered in the differential diagnosis of multiple enhancing dural based tumours.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2020.03.020DOI Listing
August 2020

Prognostic Utility of Optical Coherence Tomography for Long-Term Visual Recovery Following Pituitary Tumor Surgery.

Am J Ophthalmol 2020 10 10;218:247-254. Epub 2020 Jun 10.

Department of Ophthalmology, New Zealand National Eye Centre, University of Auckland, Auckland, New Zealand. Electronic address:

Purpose: To investigate the association between optical coherence tomography (OCT) parameters and long-term visual recovery following optic chiasm decompression surgery.

Design: Prospective cohort study.

Methods: Consecutive patients who underwent pituitary or parasellar tumor resection between January 2009 to December 2018 were recruited in a single-center, 2-year prospective, longitudinal cohort study. Best-corrected visual acuity, visual fields, and OCT retinal nerve fiber layer (RNFL) thickness, macular thickness and volume were assessed preoperatively, and at 6 weeks, 6 months, and 2 years postoperatively. Long-term visual field recovery and maintenance were defined as a mean deviation of >-3 at 24 months, and visual acuity recovery and maintenance were defined as a logarithm of minimal angle of resolution (logMAR) of 0 (Snellen 20/20) or better at 24 months.

Results: A total of 239 patients (129 men, 110 women; mean ± SD age: 52 ± 16 years) were included. Multiple logistic regression analysis demonstrated that increased inferior RNFL thickness (per 10 μm) was associated with higher odds of long-term visual field recovery and maintenance (odds ratio [OR]: 1.26; 95% confidence interval [CI]: 1.12-1.41; Q < 0.001), and greater superior RNFL thickness (per 10 μm) was associated with higher odds of visual acuity recovery and maintenance (OR: 1.13; 95% CI: 1.03-1.27; Q = 0.031). A multivariable risk prediction model developed for long-term visual field recovery and maintenance that incorporated age, preoperative visual function, and RNFL thickness demonstrated C-statistics of 0.83 (95% CI: 0.72-0.94).

Conclusion: Preoperative RNFL thickness was associated with long-term visual recovery and maintenance following chiasmal decompression. The multivariable risk prediction model developed in the present study may assist with preoperative patient counseling and prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajo.2020.06.004DOI Listing
October 2020

Spontaneous symptomatic orbital meningoencephalocele in an adult patient. Case report and review of the literature.

J Clin Neurosci 2020 Jul 11;77:224-226. Epub 2020 May 11.

Department of Neurosurgery. Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

Symptomatic spontaneous meningoencephalocele (MEC) is a very rare entity in adults and there have been no reported cases of spontaneous MEC through the orbital roof in an adult. We report a 41-year-old woman who presented with a left eyelid swelling for several weeks without any history of trauma. Brain magnetic resonance imaging (MRI) showed a MEC through the orbital roof causing a significant blepharocele in this young patient. Supraorbital craniotomy was performed to repair the bone defect. The symptoms resolved immediately after surgery. Even though blepharocele is a rare manifestation of spontaneous orbital MEC it should be considered in the differential diagnosis for appropriate surgical management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2020.05.020DOI Listing
July 2020

The oblique occipital sinus - implications in posterior fossa approaches.

J Clin Neurosci 2020 Jun 18;76:202-204. Epub 2020 Apr 18.

Department of Neurosurgery, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.

The retrosigmoid craniotomy is the standard approach to resect pathologies in the cerebellopontine angle (CPA). Following the craniotomy, the dura mater is opened in the inferolateral direction and the basal cistern arachnoid is dissected in order to release pressure by the outflow of cerebrospinal fluid (CSF) from the foramen magnum, so that the CPA compartment can be approached with minimal retraction of the cerebellum. We report two patients, both with vestibular schwannoma, in whom preoperative magnetic resonance imaging (MRI) revealed unusual large oblique occipital sinus (OOS) draining laterally into the sigmoid sinus - jugular bulb junction. The sinuses were preserved intact while dura mater was opened for CSF release. Careful preoperative imaging is essential prior to posterior fossa lesions approaches in order to evaluate the persistency of an OOS, especially in a retrosigmoid approach. Inadvertent OOS damage might result in, not only significant bleeding during dural opening, but also air embolism or venous hypertension, if the contralateral sigmoid sinus is small or absent.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2020.04.055DOI Listing
June 2020

Repeated spontaneous intra-tumoural and subarachnoid haemorrhage in an anticoagulated patient with a previously-irradiated vestibular Schwannoma: Case report.

J Clin Neurosci 2020 Mar 28;73:323-325. Epub 2019 Dec 28.

Department of Neurosurgery, Hadassah Hebrew University Medical Centre, Jerusalem, Israel; Department of Surgery, The University of Melbourne, Melbourne, Australia.

Subarachnoid hemorrhage caused by vestibular schwannomas (VS) is rare with no clear pathological mechanism supported in the existing literature. However, anticoagulation treatment as well as previous radiation therapy appear to be a crucial risk factor for subarachnoid haemorrhage from a VS. We report an unusual case of both intratumoural and subarachnoid haemorrhage in a patient with a VS on anticoagulation treatment previously treated with stereotactic radiosurgery. We emphasize the need for caution when considering the use of radiation therapy for treatment of VS in patients on chronic anticoagulation therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2019.11.018DOI Listing
March 2020

Extracellular vesicles and their role in glioblastoma.

Crit Rev Clin Lab Sci 2019 Dec 22:1-26. Epub 2019 Dec 22.

Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, Australia.

Research on the role of extracellular vesicles (EVs) in disease pathogenesis has been rapidly growing over the last two decades. As EVs can mediate intercellular communication, they can ultimately facilitate both normal and pathological processes through the delivery of their bioactive cargo, which may include nucleic acids, proteins and lipids. EVs have emerged as important regulators of brain tumors, capable of transferring oncogenic proteins, receptors, and small RNAs that may support brain tumor progression, including in the most common type of brain cancer, glioma. Investigating the role of EVs in glioma is crucial, as the most malignant glioma, glioblastoma (GBM), is incurable with a dismal median survival of 12-15 months. EV research in GBM has primarily focused on circulating brain tumor-derived vesicles in biofluids, such as blood and cerebrospinal fluid (CSF), investigating their potential as diagnostic and prognostic biomarkers. Gaining a greater understanding of the role of EVs and their cargo in brain tumor progression may contribute to the discovery of novel diagnostics and therapeutics. In this review, we summarize the known and emerging functions of EVs in glioma biology and pathogenesis, as well as their emerging biomarker potential.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/10408363.2019.1700208DOI Listing
December 2019

Therapeutic Targeting of Cancer Stem Cells in Human Glioblastoma by Manipulating the Renin-Angiotensin System.

Cells 2019 10 31;8(11). Epub 2019 Oct 31.

Gillies McIndoe Research Institute, Wellington 6021, New Zealand.

Patients with glioblastoma (GB), a highly aggressive brain tumor, have a median survival of 14.6 months following neurosurgical resection and adjuvant chemoradiotherapy. Quiescent GB cancer stem cells (CSCs) invariably cause local recurrence. These GB CSCs can be identified by embryonic stem cell markers, express components of the renin-angiotensin system (RAS) and are associated with circulating CSCs. Despite the presence of circulating CSCs, GB patients rarely develop distant metastasis outside the central nervous system. This paper reviews the current literature on GB growth inhibition in relation to CSCs, circulating CSCs, the RAS and the novel therapeutic approach by repurposing drugs that target the RAS to improve overall symptom-free survival and maintain quality of life.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cells8111364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912312PMC
October 2019

Multilayered Heterogeneity of Glioblastoma Stem Cells: Biological and Clinical Significance.

Adv Exp Med Biol 2019 ;1139:1-21

Department of Surgery, The University of Melbourne, Parkville, VIC, Australia.

Glioblastoma is a primary tumor of the brain with a poor prognosis. Pathological examination shows that this disease is characterized by intra-tumor morphological heterogeneity, while numerous and ongoing genomic analysis reveals multiple layers of heterogeneity. Intra-tumor and patient-to-patient heterogeneity is underpinned by cellular, genetic, and molecular heterogeneity, which is thought to be key determinants of time to tumor recurrence and resistance to therapy. The key cell type believed to contribute to the establishment and ongoing evolution of tumor heterogeneity is a glioma stem cell (GSC) subpopulation. In this chapter, we review, highlight, and discuss controversies and clinical relevance of glioblastoma heterogeneity and its cellular basis. Characterization of how cancer stem cells (CSCs) behave is important in understanding how tumors are initiated and how they recur following initial treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-3-030-14366-4_1DOI Listing
August 2019

Understanding and exploiting cell signalling convergence nodes and pathway cross-talk in malignant brain cancer.

Cell Signal 2019 05 30;57:2-9. Epub 2019 Jan 30.

Department of Microbiology and Immunology, The University of Melbourne, Melbourne, VIC 3000, Australia; Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia. Electronic address:

In cancer, complex intracellular and intercellular signals constantly evolve for the advantage of the tumour cells but to the disadvantage of the whole organism. Decades of intensive research have revealed the critical roles of cellular signalling pathways in regulating complex cell behaviours which influence tumour development, growth and therapeutic response, and ultimately patient outcome. Most studies have focussed on specific pathways and the resulting tumour cell function in a rather linear fashion, partly due to the available methodologies and partly due to the traditionally reductionist approach to research. Advances in cancer research, including genomic technologies have led to a deep appreciation of the complex signals and pathway interactions operating in tumour cells. In this review we examine the role and interaction of three major cell signalling pathways, PI3K, MAPK and cAMP, in regulating tumour cell functions and discuss the prospects for exploiting this knowledge to better treat difficult to treat cancers, using glioblastoma, the most common and deadly malignant brain cancer, as the example disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cellsig.2019.01.011DOI Listing
May 2019

Tumour stem cells in schwannoma: A review.

J Clin Neurosci 2019 Apr 6;62:21-26. Epub 2019 Jan 6.

Gillies McIndoe Research Institute, Wellington, New Zealand.

Schwannoma is a peripheral nerve tumour, accounting for 5% of benign soft tissue tumours, with vestibular schwannoma comprising 6% of all intracranial tumours. The tumour stem cell concept is rapidly gaining traction underscoring the understanding of tumourigenesis. It proposes a small subpopulation of primitive cells as the origin of the tumour and these cells account for treatment resistance, local recurrence and distant metastasis in malignant tumours. This review outlines the stem cell markers used to identify and characterise stem cells and progenitor cells in tumours and examines current evidence of the presence of tumour stem cells in schwannoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2018.12.022DOI Listing
April 2019

Circulating tumor stem cells and glioblastoma: A review.

J Clin Neurosci 2019 Mar 6;61:5-9. Epub 2019 Jan 6.

Gillies McIndoe Research Institute, Wellington, New Zealand.

Glioblastoma (GB) is the most aggressive primary brain tumor in adults. The aggressive nature of GB has been attributed to the presence of cancer stem cells (CSCs) which drive tumorigenesis and are thought to be the root cause of the disease. Circulating tumor stem cells (CTSCs), which can be derived from CSCs, have been identified in numerous types of cancer including GB, have been proposed to contribute to local and distant recurrence. There are many technical difficulties in studying CTSCs, therefore there is a significant gap in the literature pertaining to how they arise and function, and how the understanding of the biology of CTSCs could elucidate the underlying cause of local recurrence and metastasis. An initial epithelial-to-mesenchymal transition (EMT) followed by mesenchymal-to-epithelial transition involving these primitive cells appear to be the critical processes underpinning metastasis. This review focuses on the association between CSCs undergoing EMT to become CTSCs, and how this could arise from the CSC subpopulation in GB, and contribute to the understanding of the pathogenesis and treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jocn.2018.12.019DOI Listing
March 2019

Metabolic patterns and seizure outcomes following anterior temporal lobectomy.

Ann Neurol 2019 02 17;85(2):241-250. Epub 2019 Jan 17.

Departments of Medicine and Neurology, Melbourne Brain Centre, University of Melbourne, Royal Melbourne Hospital, Melbourne, Victoria, Australia.

Objective: We investigated the relationship between the interictal metabolic patterns, the extent of resection of F-fluorodeoxyglucose positron emission tomography ( FDG-PET) hypometabolism, and seizure outcomes in patients with unilateral drug-resistant mesial temporal lobe epilepsy (MTLE) following anterior temporal lobe (TL) resection.

Methods: Eighty-two patients with hippocampal sclerosis or normal magnetic resonance imaging (MRI) findings, concordant FDG-PET hypometabolism, and at least 2 years of postoperative follow-up were included in this 2-center study. The hypometabolic regions in each patient were identified with reference to 20 healthy controls (p < 0.005). The resected TL volume and the volume of resected TL PET hypometabolism (TLH) were calculated from the pre- and postoperative MRI scans coregistered with interictal FDG-PET.

Results: Striking differences in metabolic patterns were observed depending on the lateralization of the epileptogenic TL. The extent of the ipsilateral TLH was significantly greater in left MTLE patients (p < 0.001), whereas right MTLE patients had significantly higher rates of contralateral (CTL) TLH (p = 0.016). In right MTLE patients, CTL hypometabolism was the strongest predictor of an unfavorable seizure outcome, associated with a 5-fold increase in the likelihood of seizure recurrence (odds ratio [OR] = 4.90, 95% confidence interval [CI] = 1.07-22.39, p = 0.04). In left MTLE patients, greater extent of resection of ipsilateral TLH was associated with lower rates of seizure recurrence (p = 0.004) in univariate analysis; however, its predictive value did not reach statistical significance (OR = 0.96, 95% CI = 0.90-1.02, p = 0.19).

Interpretation: The difference in metabolic patterns depending on the lateralization of MTLE may represent distinct epileptic networks in patients with right versus left MTLE, and can guide preoperative counseling and surgical planning. Ann Neurol 2019; 1-10 ANN NEUROL 2019;85:241-250.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ana.25405DOI Listing
February 2019

Cell quiescence correlates with enhanced glioblastoma cell invasion and cytotoxic resistance.

Exp Cell Res 2019 01 15;374(2):353-364. Epub 2018 Dec 15.

Department of Surgery (RMH), The University of Melbourne, Parkville VIC 3010, Australia; Department of Microbiology & Immunology, The University of Melbourne, Parkville 3010, Australia. Electronic address:

Glioblastoma (GBM) tumor cells exhibit drug resistance and are highly infiltrative. GBM stem cells (GSCs), which have low proliferative capacity are thought to be one of the sources of resistant cells which result in relapse/recurrence. However, the molecular mechanisms regulating quiescent-specific tumor cell biology are not well understood. Using human GBM cell lines and patient-derived GBM cells, Oregon Green dye retention was used to identify and isolate the slow-cycling, quiescent-like cell subpopulation from the more proliferative cells in culture. Sensitivity of cell subpopulations to temozolomide and radiation, as well as the migration and invasive potential were measured. Differential expression analysis following RNAseq identified genes enriched in the quiescent cell subpopulation. Orthotopic transplantation of cells into mice was used to compare the in vivo malignancy and invasive capacity of the cells. Proliferative quiescence correlated with better TMZ resistance and enhanced cell invasion, in vitro and in vivo. RNAseq expression analysis identified genes involved in the regulation cell invasion/migration and a three-gene signature, TGFBI, IGFBP3, CHI3L1, overexpressed in quiescent cells which correlates with poor GBM patient survival.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.yexcr.2018.12.010DOI Listing
January 2019

The role of interleukin-6-STAT3 signalling in glioblastoma.

Oncol Lett 2018 Oct 27;16(4):4095-4104. Epub 2018 Jul 27.

Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, VIC 3050, Australia.

Glioblastoma is the most common type of malignant brain tumor among adults and is currently a non-curable disease due primarily to its highly invasive phenotype, and the lack of successful current therapies. Despite surgical resection and post-surgical treatment patients ultimately develop recurrence of the tumour. Several signalling molecules have been implicated in the development, progression and aggressiveness of glioblastoma. The present study reviewed the role of interleukin (IL)-6, a cytokine known to be important in activating several pro-oncogenic signaling pathways in glioblastoma. The current study particularly focused on the contribution of IL-6 in recurrent glioblastoma, with particular focus on glioblastoma stem cells and resistance to therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/ol.2018.9227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6144698PMC
October 2018

Inhibition of Radiation and Temozolomide-Induced Invadopodia Activity in Glioma Cells Using FDA-Approved Drugs.

Transl Oncol 2018 Dec 13;11(6):1406-1418. Epub 2018 Sep 13.

Department of Surgery, The University of Melbourne, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia; Department of Neurosurgery, The Royal Melbourne Hospital, Parkville, Victoria 3050, Australia. Electronic address:

The most common primary central nervous system tumor in adults is the glioblastoma multiforme (GBM). The highly invasive nature of GBM cells is a significant factor resulting in the inevitable tumor recurrence and poor patient prognosis. Tumor cells utilize structures known as invadopodia to faciliate their invasive phenotype. In this study, utilizing an array of techniques, including gelatin matrix degradation assays, we show that GBM cell lines can form functional gelatin matrix degrading invadopodia and secrete matrix metalloproteinase 2 (MMP-2), a known invadopodia-associated matrix-degrading enzyme. Furthermore, these cellular activities were augmented in cells that survived radiotherapy and temozolomide treatment, indicating that surviving cells may possess a more invasive phenotype posttherapy. We performed a screen of FDA-approved agents not previously used for treating GBM patients with the aim of investigating their "anti-invadopodia" and cytotoxic effects in GBM cell lines and identified a number that reduced cell viability, as well as agents which also reduced invadopodia activity. Importantly, two of these, pacilitaxel and vinorelbine tartrate, reduced radiation/temozolomide-induced invadopodia activity. Our data demonstrate the value of testing previously approved drugs (repurposing) as potential adjuvant agents for the treatment of GBM patients to reduce invadopodia activity, inhibit GBM cell invasion, and potentially improve patient outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tranon.2018.08.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6140414PMC
December 2018