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Biomedical subjects

Michael R Chicoine

Publications and source records attributed to Michael R Chicoine.

14 recordsLinked to original sources
PubMed2006

Clinical features and outcome in North American adults with moyamoya phenomenon.

BACKGROUND AND PURPOSE: To describe baseline clinical features and outcomes of adults with moyamoya phenomenon treated at a single North American institution. METHODS: We identified 34 adults with moyamoya phenomenon by review of angiographic records. Clinical presentation and baseline stroke risk factors were obtained by chart review. Follow-up was obtained prospectively. A 5-year Kaplan-Meier stroke risk was calculated. RESULTS: The median age was 42 (range 20 to 79) years. Twenty-five were women. The initial symptom was ischemia, hemorrhage, or asymptomatic in 24, 7, and 3 patients, respectively. Twenty-two had bilateral involvement and 12 had unilateral moyamoya vessels. Baseline stroke risk factors were similar between groups. The median follow-up in 31 living patients was 5.1 (range 0.2 to 19.6) years. Fourteen patients were treated with surgical revascularization (20 total hemispheres). In medically treated symptomatic hemispheres, the 5-year risk of recurrent ipsilateral stroke was 65% after the initial symptom and 27% after angiographic diagnosis. Patients with bilateral involvement presenting with ischemic symptoms were at the highest risk of subsequent stroke (n=17, 5-year risk of stroke with medical treatment after first symptom of 82%). In surgically treated hemispheres, the 5-year risk of perioperative or subsequent ipsilateral stroke or death was 17%. This was significantly different compared with medical treatment after first symptom (P=0.02) but not after angiographic diagnosis. CONCLUSIONS: Moyamoya phenomenon in North American adults is associated with a high risk of recurrent stroke, particularly those with bilateral involvement and ischemic symptoms. These data suggest a potential benefit with surgery if diagnosis could be made earlier.

Adult↗
PubMed2005

Integrative genomic analysis identifies NDRG2 as a candidate tumor suppressor gene frequently inactivated in clinically aggressive meningioma.

Although meningiomas are common central nervous system tumors, little is known about the genetic events responsible for malignant progression. In this study, we employed gene expression profiling to identify transcripts whose expression was lost in anaplastic (WHO grade III) versus benign (WHO grade I) meningioma. Approximately 40% of genes down-regulated in anaplastic meningioma were localized to chromosomes 1p and 14q. One specific gene located at 14q11.2, NDRG2, was consistently down-regulated in grade III meningioma, a finding which we validated at both the transcript and protein levels in independent sets of clinically and pathologically diverse meningiomas. Loss of NDRG2 expression was also seen in a subset of lower-grade meningiomas, including atypical meningiomas (WHO grade II) with clinically aggressive behavior. Furthermore, we found that the loss of NDRG2 expression was significantly associated with hypermethylation of the NDRG2 promoter. Collectively, these data identify NDRG2 as the first specific candidate tumor suppressor gene on chromosome 14q that is inactivated during meningioma progression. In addition, these findings highlight the utility of combining genomic, epigenetic, and expression data to identify clinically significant tumor biomarkers, and suggest that NDRG2 expression will be a useful and functionally relevant biomarker to predict aggressive behavior in patients with meningioma.

Base Sequence↗
PubMed2005

High throughput screening of meningioma biomarkers using a tissue microarray.

Meningiomas are histologically and clinically diverse CNS neoplasms with few available immunohistochemical markers of differentiation and progression. Therefore, we investigated a panel of potentially useful meningioma-associated biomarkers using high throughput tissue microarray immunohistochemistry (TMA-IHC) with a TMA that includes 9 hemangiopericytomas (HPCs) and 41 meningiomas spanning all grades, as well as two subsets of atypical meningiomas, stratified according to clinical behavior. Antibodies utilized were progesterone receptor (PR), epithelial membrane antigen (EMA), cathepsin D, E-cadherin, platelet derived growth factor (PDGF) receptor beta, PDGF BB ligand, survivin, epithelial growth factor receptor (EGFR), and vascular endothelial growth factor (VEGF). In most cases, frequencies of tumor positivity were similar to those previously reported using whole section IHC. EMA, E-cadherin, and PDGFR-beta staining patterns distinguished the anaplastic meningiomas from the HPCs (P < 0.001, P = 0.02, P = 0.015, respectively). As in prior studies, PR and cathepsin D expression were inversely proportional to tumor grade. However, PR and EGFR were also differentially expressed between symptomatic, surgically resected benign meningiomas and incidental meningiomas found at autopsy. We conclude that (1) TMA-IHC is an accurate and efficient way to rapidly assess biomarkers in meningeal tumors, (2) EMA, E-cadherin, and PDGFR-beta are useful in distinguishing anaplastic meningiomas from HPCs, and (3) the expression patterns for incidental meningiomas differ slightly from their surgically resected symptomatic counterparts.

Biomarkers, Tumor↗
PubMed2005

Why are systemic glioblastoma metastases rare? Systemic and cerebral growth of mouse glioblastoma.

BACKGROUND: Systemic metastasis of glioblastoma multiforme (GBM) in the form of bulk tumor is rare. This could be because of patient death before clinically detectable systemic metastasis, impediments to systemic egress, or the inability of GBM to grow outside the central nervous system (CNS). In the present paper, we tested this last hypothesis. METHODS: The delayed brain tumor (DBT) cell was characterized with respect to in vitro and in vivo morphology, growth rate, anchorage-independent growth, glial fibrillary acidic protein expression and cytogenetic analysis, and major histocompatibility complex (MHC) typing. We then assayed implantation-induced intracerebral and systemic GBM growth using 3 rodent models with increasing relative immunologic differences between implanted DBT cells and hosts (Balb/c mice, an isograft, MHC I H2, class type D; C3H mice, an allograft; Wistar rats, a xenograft). RESULTS: After implantation in the brain, DBT cells generated tumors that were similar to human GBM. Intracerebral DBT implantation as an isograft or allograft produced only intracranial tumors, whereas intracerebral and systemic implantation as a xenograft produced no tumors. Systemic isograft implantation yielded only systemic tumors. Systemic implantation as allografts produced only transient subcutaneous masses. CONCLUSIONS: Delayed brain tumor cells implanted outside the CNS formed tumors unless there was a significant difference between the immunotype of the implanted cells and host. These results support the hypothesis that the rarity of systemic GBM tumors lies in the presence of physical barriers and/or systemic hurdles that prevent their timely growth. These results also demonstrate that GBMs are antigenic, although not immunogenic, with their syngeneic host. Therefore, GBM may be amenable to targeted immunotherapy given successful artificial priming of the immune system.

Animals↗
PubMed2005

Ventricular catheter tack-down suture: technical note.

Tubing migration accounts for a significant number of shunt complications. In an attempt to reduce the likelihood of disconnection and tubing migration, we have developed a technique to rigidly fix the proximal catheter to the skull. The method involves the placement of a small twist drill hole adjacent to the catheter burr hole through which a suture is passed. The suture is then used to rigidly bind the proximal shunt tubing and valve to the skull. This approach provides an efficient and effective means for reducing complications related to shunt tubing migration.

Cerebral Ventricles↗
PubMed2005

Tissue transglutaminase 2 inhibition promotes cell death and chemosensitivity in glioblastomas.

Tissue transglutaminase 2 belongs to a family of transglutaminase proteins that confers mechanical resistance from proteolysis and stabilizes proteins. Transglutaminase 2 promotes transamidation between glutamine and lysine residues with the formation of covalent linkages between proteins. Transglutaminase 2 also interacts and forms complexes with proteins important in extracellular matrix organization and cellular adhesion. We have identified the novel finding that treatment of glioblastoma cells with transglutaminase 2 inhibitors promotes cell death and enhances sensitivity to chemotherapy. Treatment with either the competitive transglutaminase 2 inhibitor, monodansylcadaverine, or with highly specific small-molecule transglutaminase 2 inhibitors, KCA075 or KCC009, results in induction of apoptosis in glioblastoma cells. Treatment with these transglutaminase 2 inhibitors resulted in markedly decreased levels of the prosurvival protein, phosphorylated Akt, and its downstream targets. These changes promote a proapoptotic profile with altered levels of multiple intracellular proteins that determine cell survival. These changes include decreased levels of the antiapoptotic proteins, survivin, phosphorylated Bad, and phosphorylated glycogen synthetase kinase 3beta (GSK-3beta), and increased levels of the proapoptotic BH3-only protein, Bim. In vivo studies with s.c. murine DBT glioblastoma tumors treated with transglutaminase 2 inhibitors combined with the chemotherapeutic agent, N-N'-bis (2-chloroethyl)-N-nitrosourea (BCNU), decreased tumor size based on weight by 50% compared with those treated with BCNU alone. Groups treated with transglutaminase 2 inhibitors showed an increased incidence of apoptosis determined with deoxynucleotidyl transferase-mediated biotin nick-end labeling staining. These studies identify inhibition of transglutaminase 2 as a potential target to enhance cell death and chemosensitivity in glioblastomas.

Animals↗
PubMed2005

Subarachnoid hemorrhage caused by posterior inferior cerebellar artery aneurysm with an anomalous course of the atlantoaxial segment of the vertebral artery. Case report and review of literature.

Various anatomical courses of the vertebral artery (VA) and posterior inferior cerebellar artery (PICA) have been described. The authors present a unique case of a subarachnoid hemorrhage resulting from an aneurysm in a patient with an anatomical variation of the extracranial portion of the VA and cervical origin of the PICA. The surgical implications of this variant are discussed, and the pertinent literature reviewed. Subarachnoid hemorrhage caused by rupture of a PICA aneurysm is reported for the first time in association with a rare variation of the course of the VA.

Cerebellum↗
PubMed2003

Albumin-binding MR blood pool agents as MRI contrast agents in an intracranial mouse glioma model.

Intravenous MRI contrast agents are commonly used to improve the detection of intracranial tumors and other central nervous system (CNS) lesions for diagnosis and treatment planning. Two small-molecule, albumin-binding blood pool contrast agents (MP-2269 and MS-325) of potential clinical significance were evaluated at 1.5 Tesla in a mouse glioma model and compared with an extracellular contrast agent (OptiMARK). Tumor image contrast was significantly enhanced and long-lived following administration of 30 micromole/kg of the blood pool agents: specifically, contrast enhancement peaked slowly at 25-30 min following administration, remained constant for >3 hr, and returned to baseline within 20 hr. Comparable but "transient" enhancement was achieved using 100 micromole/kg OptiMARK: specifically, contrast enhancement peaked rapidly at 2-5 min following administration and then declined over 40 min. The blood pool contrast agents demonstrated an approximately threefold increased dose-effectiveness and a lengthened window of tumor contrast enhancement in comparison to commonly available extracellular contrast agents. This demonstrates the potential of alternative contrast-enhanced (CE) MRI examination protocols for tumor detection.

Albumins↗
PubMed2003

Analysis of the antitumoral mechanisms of lipopolysaccharide against glioblastoma multiforme.

Our objective was to analyze the lipopolysaccharide (LPS) antitumoral effect upon glioblastoma, including whether the lipid A subunit alone can elicit glioblastoma regression, whether dexamethasone suppresses this response to LPS, whether B and T lymphocytes factor in this response, and whether this antitumoral effect of LPS provides resistance against subsequent challenge with glioblastoma. Mice (BALB/c, nude or SCID) implanted with s.c. DBT glioblastomas were treated with LPS (with or without dexamethasone) or with lipid A. A subset of BALB/c mice in which s.c. DBT glioblastomas had previously been eradicated using LPS were re-implanted with s.c. or intracranial (i.c.) DBT cells. For mice with s.c. tumors, mean tumor masses (MTM) were compared between groups. Survival was compared for mice with i.c. tumors. Lipid A caused near complete tumor regression of DBT glioblastomas in BALB/c mice (p<0.0001). Dexamethasone did not alter the antitumoral effect of LPS (p=0.48). LPS reduced the MTM of s.c. glioblastomas in T lymphocyte-deficient nude mice, but not as effectively as in immunocompetent mice. The antitumoral response to LPS for T and B lymphocyte-deficient SCID mice bearing DBT glioblastomas was similar to that for nude mice. Eradication of s.c. DBT glioblastoma in BALB/c provided partial resistance to subsequent challenge with s.c. or i.c. glioblastoma. We conclude that the LPS-mediated antitumoral response against glioblastoma is dependent upon the lipid A subunit of LPS, partially dependent upon T lymphocytes, independent of B lymphocytes, unaffected by dexamethasone and provides partial protection against subsequent challenges with glioblastoma.

Animals↗
PubMed2002

Molecular characterization of human meningiomas by gene expression profiling using high-density oligonucleotide microarrays.

Meningiomas are common central nervous system neoplasms that exhibit remarkably diverse histopathology and biological behavior. Compared to astrocytomas, the most common central nervous system tumor, little is known about the molecular pathways critical for meningioma tumor formation and malignant progression. As an initial step toward characterizing the genetic basis of meningioma pathogenesis, we assessed cancer-related gene expression profiles of nonneoplastic leptomeningeal specimens and human meningiomas of varying World Health Organization (WHO) grade using high-density oligonucleotide microarrays. Although expression profile differences between nonneoplastic and meningioma specimens were readily discernible, the expression profile of a subset of genes could also distinguish WHO grade I from WHO grades II and III tumors. Altered expression levels of several genes identified in this study have been previously noted in meningiomas (eg, growth hormone receptor, IGFBP-7, endothelin receptor A, IGF2). However, we also identified a number of novel genes whose expression was associated with WHO grade and was confirmed by reverse transcriptase-polymerase chain reaction in a larger, independent set of meningeal tumors (n = 47). This report represents the first gene expression profiling studies of meningiomas and identifies some initial candidate genes that may provide further insights into the genetic basis for meningioma pathogenesis.

Carrier Proteins↗
PubMed2002

Long-term outcome after angioplasty for symptomatic extracranial carotid stenosis in poor surgical candidates.

BACKGROUND AND PURPOSE: The optimal treatment of patients with symptomatic carotid stenosis who are poor surgical candidates is uncertain. The purposes of this study were to report the long-term outcome after angioplasty in a series of these patients and to compare these data with historical control data from the North American Symptomatic Carotid Endarterectomy Trial (NASCET). METHODS: We identified 42 consecutive patients with >70% carotid stenosis and ipsilateral ischemic symptoms within 120 days of treatment with angioplasty. All were considered poor surgical candidates by experienced surgeons. Baseline epidemiological stroke risk factors were obtained from review of medical records. Follow-up was from clinic records and by telephone. RESULTS: Baseline epidemiological stroke risk factors were similar to those of medically treated NASCET patients. Angioplasty patients tended to have higher degrees of stenosis (45% with >90% stenosis versus 24% in NASCET) and more frequent contralateral stenosis or occlusion (30% versus 9%) than NASCET patients. Three patients suffered procedural strokes; 2 of the 3 made nearly complete recoveries. One additional patient suffered a central retinal occlusion 48 hours after angioplasty. No ipsilateral strokes occurred during the mean follow-up period of 1.7 years. Three patients were lost to follow-up. The cumulative risk of stroke was 9.5% (4 of 42) compared with 26% at 2 years for medically treated patients in NASCET. CONCLUSIONS: These pilot data suggest a beneficial effect of angioplasty for patients with high-grade symptomatic carotid stenosis who are not good surgical candidates.

Adult↗
PubMed2002

Postprocedure ischemic events after treatment of intracranial aneurysms with Guglielmi detachable coils.

OBJECT: Ischemic stroke or transient ischemic attack (TIA) may occur after the treatment of intracranial aneurysms with Guglielmi detachable coils (GDCs). The purpose of the present study is to investigate possible risk factors for thromboembolic events and to determine their frequency and time course. METHODS: The records of 178 consecutive patients with 193 treated intracranial saccular aneurysms were reviewed. A total of 159 GDC procedures were performed to treat 143 aneurysms in 133 of those patients who were in good neurological condition, allowing clinical detection of postprocedure ischemic events (TIA or stroke). The association of clinical, anatomical, and pharmacological factors with intraprocedure intraarterial thrombus and with postprocedure ischemic events was investigated by using uni- and multivariate analyses. Thrombus protruding into the parent artery was noted during six of 159 GDC procedures, resulting in a clinical deficit in one patient. No factor was associated with intraprocedure intraarterial thrombus. Ten postprocedure ischemic events occurred in nine patients. Seven events occurred within 24 hours, and three events occurred between 24 hours and 58 days. Aneurysm diameter and protruding coils were significant independent predictors of postprocedure ischemic events in multivariate analysis (both p = 0.02). The actuarial risk of stroke was 3.8%. CONCLUSIONS: Larger aneurysm diameter and protruding loops of coils are associated with postprocedure ischemic events after GDC placement. It is unlikely that GDC-treated aneurysms retain thromboembolic potential beyond 2 months.

Adult↗