Biomedical subjects

S W Coons

Publications and source records attributed to S W Coons.

At least 19 recordsLinked to original sources

PubMed2006

Cavernous malformation within a schwannoma: review of the literature and hypothesis of a common genetic etiology.

The finding of cavernous malformations within tumors of the central or peripheral nervous system is a rare occurrence. We report a case of a histologically proven cavernous malformation found within an eighth cranial nerve schwannoma in a 76-year-old man. The patient presented with progressive loss of hearing on the left, facial pain and dysesthesia. Symptoms improved significantly after the tumor was subtotally resected through a left retrosigmoid craniotomy. Including the present report, 34 cases of cavernous malformations associated with tumors of nervous system origin, 24 cases (71%) involving tumors of Schwann cell origin, and 9 cases (26%) involving gliomas have been published. The cases were classified into two forms based on the type of association. Conjoined association, in which the cavernous malformation is located within the tissue of the nervous system tumor, and discrete association, in which the cavernous malformation and nervous system tumor are in separate locations. We explore the etiology of this association and hypothesize that a common genetic pathway may be involved in a majority of these cases.

Aged↗

PubMed2006

Hypothalamic hamartomas: Correlation of MR imaging and spectroscopic findings with tumor glial content.

BACKGROUND AND PURPOSE: There is variability in the literature concerning the appearance and histology of hypothalamic hamartomas. This study correlates the MR imaging and proton MR spectroscopic properties of hypothalamic hamartomas with histopathologic findings. METHODS: Studies were performed with 3T and 1.5T scanners. Single voxel hamartoma spectra were acquired by using short-echo-time point-resolved spectroscopy sequences (PRESS). 2D PRESS chemical shift imaging (CSI) spectroscopic sequences were also obtained for comparison of tumor-derived spectra with normal gray matter of the amygdala. Sequences were used to compare choline (Cho), N-acetylaspartate (NAA), and myoinositol (mI) resonances by using a creatine (Cr) reference. Spectral ratios and T2 signal intensity ratios of the hamartomas were then compared with histopathologic findings. RESULTS: Data from single voxel spectroscopic sequences demonstrated a statistically significant decrease in NAA/Cr and an increase in mI/Cr ratios in tumor tissue when compared with values in normal gray matter of the amygdala. In addition, Cho/Cr ratios were also increased when compared with those in normal gray matter controls. Among the 14 hamartomas sampled, a spectrum of increased mI/Cr ratios was seen. Those tumors with markedly elevated mI/Cr demonstrated an increased glial component when compared with the remaining tumors. Increased glial component was also found to have a positive correlation with hyperintensity of lesions on T2-weighted images. CONCLUSION: We have identified a correlation between the glial/neuronal fraction as determined by histopathology and MR spectral and T2 hyperintensity variations among hypothalamic hamartomas.

Adolescent↗

PubMed2002

Endolymphatic sac tumor: unique features of two cases and review of the literature.

Endolymphatic sac tumors (EST) are rare intracranial tumors originating from the pars rugosa of the endolymphatic sac. Although typically described as histologically nonaggressive lesions, nevertheless they are termed adenocarcinomas and often become locally invasive. We report two patients with histologically proven EST with unique clinical features: the first pediatric case of an EST in an 11-year-old patient whose complaints started at the age of seven; and, a second patient, a 43-year-old man, the first report of metastatic EST which appeared in a remote location from the original site of surgery. Both patients underwent gamma-knife radiosurgery for recurrent tumor. This treatment has not been described previously for these tumors. Both patients have a follow-up of 7 years. Although not disease free they remain neurologically stable. We review the literature on EST.

Adenocarcinoma↗

PubMed2001

Identification and validation of P311 as a glioblastoma invasion gene using laser capture microdissection.

The mRNA expression profiles from glioblastoma cells residing at the tumor core and invasive rim of a human tumor resection were compared. From a single tumor specimen, 20,000 single cells from each region were collected by laser capture microdissection. Differential expression of 50-60 cDNA bands was detected. One of the sequences overexpressed by the invasive cells showed 99% homology to the P311 gene, the protein product of which is reported to localize at focal adhesions. Relative overexpression of P311 by invading glioblastoma cells compared with tumor core was confirmed by quantitative reverse transcription-PCR of six glioblastoma specimens after laser capture microdissection collection of rim and core cells. In vitro studies using antisense oligodeoxynucleotides and integrin activation confirmed the role of P311 in supporting migration of malignant glioma cells. Immunochemistry studies confirmed the presence of the P311 protein in tumor cells, particularly at the invasive edge of human glioblastoma specimens.

Amino Acid Sequence↗

PubMed2001

Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes: a cDNA microarray analysis.

Microarray analysis of complementary DNA (cDNA) allows large-scale, comparative, gene expression profiling of two different cell populations. This approach has the potential for elucidating the primary transcription events and genetic cascades responsible for increased glioma cell motility in vitro and invasion in vivo. These genetic determinants could become therapeutic targets. We compared cDNA populations of a glioma cell line (G112) exposed or not to a motility-inducing substrate of cell-derived extracellular matrix (ECM) proteins using two sets of cDNA microarrays of 5,700 and 7,000 gene sequences. The data were analyzed considering the level and consistency of differential expression (outliers) and whether genes involved in pathways of motility, apoptosis, and proliferation were differentially expressed when the motility behavior was engaged. Validation of differential expression of selected genes was performed on additional cell lines and human glioblastoma tissue using quantitative RT-PCR. Some genes involved in cell motility, like tenascin C, neuropilin 2, GAP43, PARG1 (an inhibitor of Rho), PLCy, and CD44, were over expressed; other genes, like adducin 3y and integrins, were down regulated in migrating cells. Many key cell cycle components, like cyclin A and B, and proliferation markers, like PCNA, were strongly down regulated on ECM. Interestingly, genes involved in apoptotic cascades, like Bcl-2 and effector caspases, were differentially expressed, suggesting the global down regulation of proapoptotic components in cells exposed to cell-derived ECM. Overall, our findings indicate a reduced proliferative and apoptotic activity of migrating cells. cDNA microarray analysis has the potential for uncovering genes linking the phenotypic aspects of motility, proliferation, and apoptosis.

Apoptosis↗

PubMed2001

Death-associated protein 3 (Dap-3) is overexpressed in invasive glioblastoma cells in vivo and in glioma cell lines with induced motility phenotype in vitro.

PURPOSE: To discover the genetic determinants of glioma invasion in vivo, we compared the mRNA expression profiles of glioblastoma cells residing at the tumor core versus those at the invasive rim of a human tumor resection. EXPERIMENTAL DESIGN: From a single glioblastoma specimen, 20,000 individual cells from each region (core and invasive rim) were collected by laser capture microdissection and analyzed by mRNA differential display. Differential expression of gene candidates was confirmed by laser capture microdissection and quantitative reverse transcription-PCR in additional glioblastoma multiforme specimens, and the role in migration was further evaluated in glioma cell lines in vitro. RESULTS: Reproducible overexpression the death-associated Protein 3 (Dap-3) mRNA (NM 004632, GenBank; also reported as human ionizing resistance conferring protein mRNA, HSU18321, GenBank) by invasive cells was identified. Although the full-length Dap-3 protein has been described as proapoptotic, the NH(2)-terminal fragment can act in a dominant negative way resulting in protection from programmed cell death. In glioma cell lines T98G and G112 with an induced motility phenotype, Dap-3 was up-regulated at the mRNA and protein level as assessed by quantitative reverse transcription-PCR, cDNA microarray, and Western blot analysis. These cells showed an increased resistance to undergo camptothecin-induced apoptosis, which was overcome by effective Dap-3-antisense treatment. Antisense treatment also decreased the migration ability of T98G cells. CONCLUSIONS: Dap-3 is up-regulated in invasive glioblastoma multiforme cells in vivo and in glioma cells with an induced motility phenotype in vitro. When migration is activated, Dap-3 is up-regulated and cells become resistant to apoptosis. These findings suggest that Dap-3 confers apoptosis-resistance when migration behavior is engaged.

Apoptosis↗

PubMed2000

Osteosarcoma of the temporal fossa with hemorrhagic presentation: case report.

OBJECTIVE AND IMPORTANCE: Excluding tumors of hematopoietic origin, osteosarcomas are the most common bone tumor, although involvement of the brain or cranial base is rare. CLINICAL PRESENTATION: A 16-year-old girl with an osteosarcoma of the temporal fossa presented with an intracerebral hemorrhage. The management strategy of this lesion, including the operative interventions, is described. INTERVENTION: Several modes of treatment were undertaken, including radical resection of the cranial base lesion and excision of the cavernous sinus after a cervical internal carotid artery-to-middle cerebral artery vein bypass graft. CONCLUSION: The patient was alive and without evidence of disease 11 months after presentation but died shortly thereafter of complications related to adjuvant therapies.

Adolescent↗

PubMed2000

Effect of voxel position on single-voxel MR spectroscopy findings.

BACKGROUND AND PURPOSE: Single-voxel MR spectroscopy is a widely used tool for evaluating brain tumors. Although extensive data are available on the MR spectral appearance of tumors, less is known about the effect of voxel position on the accuracy of single-voxel MR spectroscopy findings. The purpose of this study was to test the hypothesis that the accuracy of single-voxel MR spectroscopy in the categorization of lesions as either tumor or not tumor is dependent on voxel position. METHODS: Fifty single-voxel MR spectra acquired with a fully automated stimulated-echo spectroscopy sequence were reviewed retrospectively in 43 patients with new or previously treated intra-axial brain tumors. Spectra were analyzed for the presence of choline, creatine, N-acetylaspartate (NAA), and lipid/lactate. Choline/creatine and NAA/creatine peak area ratios were assessed qualitatively. Lesions were grouped into one of three categories on the basis of spectral pattern: tumor, not tumor, or indeterminate. Results of MR spectroscopy were compared with the final histopathologic diagnosis. RESULTS: Histologic confirmation was obtained in 19 patients; MR spectra were interpretable in 17 of those. MR spectra correctly categorized nine of 17 lesions (six tumor, three nontumor). All eight misdiagnosed lesions were tumors. When the MR spectroscopy voxel included the enhancing edge of the lesion, the spectra correctly categorized seven of eight lesions (four of five tumors and all three cases of radiation necrosis). When the MR spectroscopy voxel was positioned centrally within the lesion, the spectra correctly reflected histologic outcome in two of nine lesions (all tumors). CONCLUSION: The reliability of single-voxel MR spectroscopy findings is dependent on voxel position. Spectra obtained from voxels at the enhancing edge of a tumor more accurately reflect lesion histopathology than do spectra obtained from the lesion center, even if the centrally placed voxels contain solidly enhancing tissue.

Aspartic Acid↗

PubMed1999

Allogeneic astrocytoma in immune competent dogs.

We have induced in canines long-term immune tolerance to an allogeneic cell line derived from a spontaneous canine astrocytoma. Allogeneic astrocytoma cells were implanted endoscopically into the subcutaneous space of fetal dogs before the onset of immune competency (< 40th gestational day). At adulthood, dogs rendered tolerant successfully serve as recipients of intracranial transplants of their growing allogeneic, subcutaneous tumor. Transplanted dogs subsequently develop a solid brain tumor with histological features similar to the original astrocytoma. This model may allow rapid development and evaluation of new therapies for brain tumors, as well as afford tumor biology studies that are untenable in smaller, immune incompetent, or inbred animals harboring less representative tumors.

Animals↗

PubMed1999

Sporadic unifocal infantile myofibromatosis involving the skull. Case report.

Infantile myofibromatosis involving the skull is a benign disease if there is a solitary lesion. However, the multifocal form with skull involvement may portend a lethal course in the 1st year of life if there is involvement of the heart, lungs, or gastrointestinal tract. The authors report the case of a 3-year-old boy with an enlarging left parietal skull lesion that had been present since infancy. Increasing pain and the need to obtain tissue for diagnosis led to resection of the lesion by means of a small craniectomy. Further evaluation revealed no other lesions. A distinctly rare disease is presented, and the need for staging in children younger than 2 years of age is suggested to rule out cardiac, pulmonary, or gastrointestinal involvement.

Child, Preschool↗

PubMed1999

Plexiform neurofibroma of the cauda equina. Case report.

Plexiform neurofibroma of the cauda equina has been reported only twice previously. The authors report the first pediatric patient in whom such a tumor has been found. A 4-year-old boy presented with low-back pain that radiated bilaterally into the L-4 and L-5 dermatomes. A dermal sinus noted at the midthoracic level was surrounded by a hemangiomatous lesion. Magnetic resonance imaging confirmed the presence of the dermal sinus and revealed a well-defined lumbosacral mass that showed heterogeneous intensity with irregular enhancement. Intraoperatively, a solid mass, which engulfed the entire cauda equina, could not be dissected from the roots. The dermal sinus tract, however, was excised from the thoracic spine. The patient underwent radiotherapy to control the tumor and relieve his pain. Plexiform neurofibromas of the cauda equina are characterized by an insidious and progressive clinical course. The tumor mass may engulf all the roots of the cauda equina. No plexiform neurofibroma of the cauda equina has been reported to be associated with neurofibromatosis Type 1. The authors assume that the thoracic-level dermal sinus observed in this child was an incidental finding.

Cauda Equina↗

PubMed1999

Pathology of intracranial neoplasms.

This article discusses the gross and microscopic pathology of intracranial neoplasms. Primary intracranial neoplasms include tumors of the brain parenchyma; meninges; and rest of mesenchymal, epithelial, and germ cell derivation. The concept of tumor malignancy for primary central nervous system (CNS) neoplasms is somewhat different from that for systemic tumors. Although the capacity to metastasize is a defining feature of systemic malignancies and metastasis to the brain is a relatively common occurrence, primary CNS neoplasms rarely metastasize outside the CNS.

Brain Neoplasms↗

PubMed1998

Mitosis identification in diffuse gliomas: implications for tumor grading.

BACKGROUND: The histologic differentiation of mitotic figures is a cornerstone of several highly predictive grading systems for gliomas. In some systems, the presence of even a single mitotic figure is sufficient to classify an astrocytoma as high grade. However, the extent of microscopic examination necessary to exclude the presence of significant mitotic activity has not been determined. METHODS: Hematoxylin and eosin-stained slides from 410 astrocytomas and 107 oligodendrogliomas/oligoastrocytomas were reviewed until the first mitosis was identified or 100 400x fields had been reviewed without identification of a mitosis. The number of the field in which the first mitosis was found was correlated with diagnosis, grade, and survival. RESULTS: A review of 50 400x fields was necessary to achieve a >90% sensitivity in identifying a mitosis in a Grade 3 astrocytoma specimen, compared with 20 400x fields in anaplastic (Grade 3 and 4) oligodendroglioma specimens. For Grade 3 astrocytomas, there was a significant independent correlation between survival and the field in which the first mitosis was found (P = 0.02). For the oligodendroglial tumors, there was a strong correlation between the number of fields counted until the first mitosis was found and grade (P < 0.0001). CONCLUSIONS: The evaluation of mitotic activity offers more prognostic information than can be obtained by the simple approach of noting only their presence or absence. Data were acquired regarding the diligence of the microscopic examination necessary to evaluate the presence or absence of mitotic activity. A 1 cm x 0.1 cm needle biopsy contains adequate tissue to evaluate mitotic activity for the purpose of histologic grading; however, this adequacy is dependent on the sample's being representative and composed entirely of cellular tumor.

Biopsy↗

PubMed1997

Improving diagnostic accuracy and interobserver concordance in the classification and grading of primary gliomas.

BACKGROUND: Accurate histologic diagnosis of gliomas is fundamental to proper patient management and to the interpretation of basic and clinical investigations. Diagnostic accuracy and reproducibility are compromised by the subjective histologic criteria currently used to classify and grade gliomas. METHODS: The histologic features of 4 sets of gliomas (a total of 244 cases) were reviewed independently by 4 neuropathologists to determine interobserver diagnostic concordance rates. Cases wherein diagnostic disagreements arose were reviewed jointly to identify and refine the histologic criteria that were adversely affecting diagnostic reproducibility. Using the criteria developed in the study, a set of 315 gliomas with known survival data was evaluated in order to validate the usefulness of the criteria. RESULTS: There was significant improvement in diagnostic concordance with each session (P = 0.02). For the first session, the concordance rates were as follows: all 4 reviewers, 52%; any 3 reviewers, 60%; 2 reviewers, 70%. For the fourth session, the respective rates were 69%, 75%, and 80%. Although features important in grading, particularly microvascular proliferation, were sometimes problematic, most disagreements related to the classification of tumors. Much of the improvement related to the refinement of criteria distinguishing diffuse astrocytomas from oligodendrogliomas/oligoastrocytomas and pilocytic astrocytomas. It was concluded that the presence of any typical oligodendroglioma was sufficient to remove a tumor from the astrocytoma category. CONCLUSIONS: The authors' data indicate that oligodendroglial tumors comprise up to 25% of gliomas, a significantly higher proportion than was previously recognized. The data also suggest that the wide range of survival times reported for patients with anaplastic astrocytoma may reflect "contamination" resulting from misdiagnosis, particularly of oligodendroglial tumors and pilocytic astrocytomas.

Brain Neoplasms↗

PubMed1997

The prognostic significance of Ki-67 labeling indices for oligodendrogliomas.

OBJECTIVE: The prognostic significance of quantitative measurement of tumor proliferative activity was evaluated for oligodendroglial tumors. METHODS: Ki-67/MIB-1 immunochemistry was used to measure proliferative activity in 81 oligodendrogliomas and oligoastrocytomas. The relationship among survival, proliferation, histological features, and clinical variables were evaluated using a Cox proportional hazards analysis. RESULTS: After stratifying by histological grade and adjusting for age at diagnosis, there was a significant association between the Ki-67/MIB-1 labeling index (LI) (percentage of positive cells) and survival (P = 0.04). This association was illustrated further by the significantly different survival of two groups based on LI ranges of less than or equal to 5 and greater than 5 (P < 0.0001). CONCLUSION: The poor correlation between mitotic figures and survival in oligodendrogliomas that has been reported previously emphasizes the need for an accurate method to measure proliferative activity. Our study demonstrated the usefulness of the Ki-67/MIB-1 LI and demonstrated that LI ranges can be defined for clinical application.

Adolescent↗

PubMed1997

Juvenile active ossifying fibroma. Report of four cases.

Juvenile active ossifying fibroma is a rare lesion seldom seen by neurosurgeons. It originates in the paranasal sinuses during childhood, grows slowly, and encroaches on adjacent orbital and cranial compartments. In the past 3 years, four patients with this lesion were seen (three men and one woman; mean age 28 years). The clinical presentations were different with each patient: sinusitis, meningitis, periorbital pain, and a unique case of a juvenile active ossifying fibroma presenting with high-grade internal carotid artery stenosis and ischemic symptoms. Three patients were treated by transfacial approaches: two with a transfrontal-nasal approach and one with a transfrontal-nasoorbital approach. Two open resections resulted in gross-total excision and no recurrence as of the 2-year follow-up review. In the third patient, the tumor-encased carotid artery was preserved at the expense of a complete resection; that patient underwent superficial temporal artery-middle cerebral artery bypass and remains without ischemic symptoms or tumor recurrence at 2 years. The fourth patient underwent three subtotal endoscopic resections and is also without symptomatic recurrence at 2 years. Three points must be made concerning these lesions. First, the clinical and radiographic characteristics of juvenile active ossifying fibroma may not be easily recognized by neurosurgeons, which could lead to misdiagnosis and mismanagement of these lesions. Second, this tumor can encase the carotid artery and cause severe stenosis or occlusion. Third, complete resection of the tumor is required to effect a cure, and transfacial approaches, which give wide exposure of the sinuses, appear to yield better, more radical resections than endoscopic procedures.

Adult↗

PubMed1997

Expression of the genes encoding myelin basic protein and proteolipid protein in human malignant gliomas.

Pathological differentiation of oligodendroglioma and mixed oligoastrocytoma from astrocytoma is difficult, relying on morphological characteristics due to the lack of reliable immunohistochemical stains. Oligodendrocytes, the presumed cell of origin of oligodendrogliomas, highly express the genes encoding myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the expression of these genes to determine whether they might be useful molecular markers of oligodendrocytic tumors. MBP and PLP were highly expressed in all oligodendrogliomas and minimally expressed in glioblastomas multiforme. MBP was highly expressed in mixed oligoastrocytomas, whereas PLP expression was minimal. The association between tumor classification and expression of the MBP and PLP genes was statistically significant. Expression of these genes may serve as a useful molecular marker for some subtypes of human gliomas.

Adult↗

PubMed1996

Dichotomy of astrocytoma migration and proliferation.

Astrocytomas often show high rates of local invasion that lead to local recurrence of the disease. Histologically, the most highly invasive astrocytoma cells are detected in isolation rather than as nests of tumor. Our study attempted to determine whether the migratory response to extracellular substrates influences the proliferative behavior of these highly invasive cells. The preferential and specific migratory response of human astrocytoma cells to extracellular matrix proteins was assessed by a microliter scale migration assay. Growth curve studies on protein ligands permissive (merosin) for cell migration indicated that the lag phase was protracted compared with cells seeded on non-permissive proteins (vitronectin). Once a certain cell density was reached, logarithmic proliferation was indistinguishable on the different proteins. The proliferation index of populations of cells migrating on merosin and vitronectin was measured by both BrdU incorporation and MIB-1 immunocytochemistry labeling. Cells seeded on vitronectin showed higher proliferation throughout the population than cells seeded on merosin. On merosin, the more migratory cells at the periphery were less proliferative than non-migratory cells in the central region of that population. The integrin-associated signal transduction protein, p125FAK, was heavily localized in the membrane of non-migrating cells and largely absent in migrating astrocytoma cells. We conclude that temporally, proliferation and migration are mutually exclusive behaviors. Cell density or non-permissive substrates that inhibit cell motility favor a more proliferative phenotype. Conversely, active migration suppresses cell proliferation.

Astrocytoma↗