Biomedical subjects

S W Coons

Publications and source records attributed to S W Coons.

At least 37 records · Page 2Linked to original sources

PubMed1996

Proliferation and motility responses of primary and recurrent gliomas related to changes in epidermal growth factor receptor expression.

Astrocytic neoplasms show a high incidence of elevated or mutated epidermal growth factor receptor (EGFR) expression. Although proliferative effects from EGFR activation are well described, the role that changes in this receptor play in glioma growth and migration remain poorly addressed. This report characterizes changes in the levels of EGFR expression in three glial tumors at initial presentation (resection) and at the time of recurrence. By quantitative flow cytometry the mean level of EGFR expression increased, decreased, or remained the same in different recurrent astrocytomas relative to their primary tumor cells. Immunocytochemistry for EGFR on monolayer cells corroborated the level of expression in the recurrent tumors relative to their matched primary specimen. Immunoprecipitation indicated that 170 kd EGFR was expressed in each of the tumors, and showed normal down regulation following treatment with EGF. Proliferation response to EGF was seen in only 1/6 instances, but was concentration-dependent when observed. Stimulated migration of the cells was frequently seen and was also concentration-dependent on EGF; the magnitude of response was related to the relative level of 170 kd EGFR expression in the cells. EGFR immunostaining of tissue sections from the tumors confirmed the levels of EGFR expressed in primary and recurrent astrocytomas as was seen in the cultured cells. These results indicate that the relative levels of EGFR in early passage cell cultures from glioma specimens concurs with the measured tissue levels of expression. Human glioma cells are more responsive to migration induction than proliferation induction by EGF.

Cell Division↗

PubMed1996

Glycolipids and myelin proteins in human oligodendrogliomas.

We studied myelin proteins and glycolipids in 24 human oligodendrogliomas (16 pure, eight mixed), including two grade I, 13 grade II, five grade III, and four grade IV. Tumours with a 1b ganglioside content (GD1b, GT1b and GQ1b) over 30% of total gangliosides occur more frequently in the WHO grade I and II (47%) and grade III (40%) than in the grade IV (25%) group; there was no difference in the amounts of total ganglioside or individual gangliosides between pure and mixed oligodendrogliomas. The presence of 6'-LM1 correlated with higher grades of tumours (chi 2 P approximately 0.02); however, 3'-LM1 and total neolacto-series gangliosides did not correlated with grade. Immunohistochemical studies of oligodendrocyte and myelin markers (GalCer, sulfatide, 2',3' -cyclic nucleotide phosphodiesterase, myelin basic protein and proteolipid protein) using specific antibodies showed only a very small proportion of tumour cells staining. These data do not support the hypothesis that tumours classified as oligodendrogliomas are derived from mature oligodendrocytes.

Brain Neoplasms↗

PubMed1996

Titanium aneurysm clips: Part I--Mechanical, radiological, and biocompatibility testing.

Most aneurysm clips are made of cobalt-based alloys. Although these clips are nonferromagnetic, they still produce artifact that degrades the quality of magnetic resonance (MR) images. A new aneurysm clip of pure titanium was developed to minimize artifact on postoperative MR images. We evaluated these clips in a series of mechanical tests in vitro, biocompatibility tests in rabbits, and radiological tests in greyhound dogs. The clip sizes and shapes matched those of conventional aneurysm clips. The average closing forces ranged between 151.6 and 181.8 g and were not diminished by repeated sterilization or stress. After > 20 million cycles of high-pressure and high-frequency pulsations, the clips did not open and the closing forces were not reduced. Titanium aneurysm clips implanted in the subarachnoid space of 12 rabbits for 1 or 6 months produced mild gliosis identical to that produced by implantation of cobalt alloy clips in 12 control rabbits. Based on pre- and postoperative weights and electron microscopic scans, the titanium implants did not corrode. The artifact on computed tomographic and MR imaging produced by a titanium clip placed on the internal carotid artery of a greyhound was less than that produced by an identical cobalt-chrome alloy clip by a factor of two to three. This study demonstrated that titanium aneurysm clips are mechanically equivalent to conventional clips, biocompatible, and corrosion resistant. Furthermore, titanium clips have superior imaging characteristics, creating less computed tomographic and MR imaging artifact and permitting better resolution of anatomic structures than cobalt alloy clips.

Animals↗

PubMed1996

Biological and molecular analysis of a low-grade recurrence of a glioblastoma multiforme.

We and others have reported that human malignant gliomas demonstrate intratumor heterogeneity in which many regions may be benign; however, the presence of regions of increased malignancy in these same tumors is generally indicative of poor patient prognosis. These data suggested that tumor progression may be a local phenomenon, resulting in regions that progress to a more malignant type prior to the progression of the entire tumor. Implicit in this premise is the idea that molecular markers of tumor progression may be detectable prior to histological evidence of progression. This report details analyses performed on a primary and recurrent tumor obtained from the same patient in which the primary tumor was of a higher histological grade than the recurrent tumor. Results of molecular, cytogenetic, flow cytometric, and histological analyses of the primary tumor were indicative of a grade 4 glioblastoma multiforme. Standard cytogenetic and flow cytometric analyses demonstrated that the cells were near-diploid with a stem line population of 46,XX normal G-banded karyotypes. In contrast, tissue resected from the recurrent tumor 5 months later was histologically less malignant; however, the molecular, cytogenetic, and flow cytometric analyses of this sample demonstrated the presence of specific genetic abnormalities typically found in more malignant tumors. These data demonstrate that specific molecular and/or genetic changes leading to tumor progression may become detectable in a glioma prior to the appearance of histological features of a higher grade tumor.

Adult↗

PubMed1995

Cytogenetic and flow cytometry DNA analysis of regional heterogeneity in a low grade human glioma.

This study combined flow cytometry with standard cytogenetic analysis of first division cells to evaluate regional heterogeneity in 38 spatially mapped regions of a low grade human oligoastrocytoma. Histologically, the tumor was relatively homogeneous. In contrast, flow cytometry and cytogenetic analyses identified variable percentages of near-diploid (ND; 35 to 57 chromosomes/metaphase) and near-tetraploid (81-103 chromosomes/metaphase) populations. The largest proportion of cells in the ND population was 46,XY with normal Giemsa bands; however, four karyotypically unrelated ND clones also were identified. The development of these clonal populations centered around a region in which more than 50% of the cells contained nonclonal abnormalities and which demonstrated more histological pleomorphism than any other region. The frequency of the nonclonal karyotypes suggested that this region was genetically unstable. Three of the clonal ND populations resided in small, spatially discreet areas of the tumor. The largest and the most widely distributed clonal population, 47,XY,+7, underwent further evolution to give rise to seven additional sidelines. This investigation demonstrates that low grade gliomas have areas of genetic instability capable of generating mutant cells with the capacity to proliferate and to form cellular foci. As a result, multiple, spatially distinct clonal populations can exist in low grade gliomas, some of which are capable of further cytogenetic evolution and clonal expansion, resulting in tumor progression.

Adult↗

PubMed1995

Correlation of ganglioside patterns of primary brain tumors with survival.

BACKGROUND: Classification/grading schemes for brain tumors are based mainly on histologic examinations, but these have major limitations, which has led to a search for more objective prognostic markers. Gangliosides have several biologic effects relevant to tumors, and ganglioside compositions of primary brain tumors correlate with diagnosis. This led to the authors' hypothesis that ganglioside patterns of brain tumors might be useful as prognostic indicators. METHODS: Gangliosides in primary brain tumors of different histologic types from 84 patients were analyzed. Specific ganglioside patterns and several other relevant variables were examined for associations with survival using a Cox proportional hazards model. Kaplan-Meier survival curves were analyzed using the log-rank test. RESULTS: Patients in whom less than 30% of total tumor gangliosides consisted of 1b pathway gangliosides (GD1b, GT1b, and GQ1b) had significantly higher risk ratios than those with more than 30% 1b gangliosides (P approximately 0.03). The presence of 6'-LM1 (NeuAc alpha 2-->6Gal beta 1-->4Glc-NAc beta 1-->3Gal beta 1-->4Glc beta 1-->1Cer was also associated with a higher risk ratio (P approximately 0.007). Combinations of 1b gangliosides and 6'-LM1 identified three groups of patients regardless of histologic diagnosis. Group A, with less than 30% 1b and the presence of 6'-LM1, had a median survival time of 331 days. Group B, with less than 30% 1b but no 6'-LM1, had a median survival time of more than 698 days. Group C, with more than 30% 1b had a median survival time of more than 776 days. CONCLUSIONS: The correlation of ganglioside patterns with survival in this initial investigation suggests the potential of 1b gangliosides and 6'-LM1 to be used as prognostic indicators. Continuing research is being conducted to assess this possibility prospectively.

Adolescent↗

PubMed1995

Anterior communicating artery aneurysm paraparesis syndrome: clinical manifestations and pathologic correlates.

OBJECTIVE: Clinicopathologic evaluation of patients with lower extremity paraparesis/-plegia following rupture and repair of anterior communicating artery (ACoA) aneurysms. DESIGN: Institution-based retrospective review. SETTING: A tertiary neurologic referral center. PATIENTS, PARTICIPANTS: Seven of 101 patients with subarachnoid hemorrhage from ruptured ACoA aneurysms treated between January 1987 and December 1992. MAIN OUTCOME MEASURES: Neurologic status at latest follow-up examination. RESULTS: All patients presented with severe hemorrhage, poor clinical grade, and intracranial hypertension. Motor deficits developed within 7 days of aneurysm rupture and persisted for a mean duration of 39 days. Angiographic evidence of vasospasm in the anterior cerebral artery (ACA) distribution was documented in all cases, and paraparesis persisted beyond the angiographic resolution of vasospasm. All patients had evidence of frontal lobe dysfunction throughout their postoperative courses, and deep venous thrombosis and pulmonary emboli were common causes of morbidity and mortality. Autopsy data supported regional microvascular ischemia within the ACA distribution as the etiology of these motor deficits. CONCLUSIONS: The combination of vasospasm in the ACA distribution and lower extremity weakness associated with cognitive and affective impairment that resolves with time is common in patients with ACoA aneurysms. We propose that this constellation of clinical, radiographic, and pathologic findings be referred to as the "ACoA aneurysm paraparesis syndrome."

Aged↗

PubMed1994

Gangliosides as diagnostic markers of human astrocytomas and primitive neuroectodermal tumors.

BACKGROUND: Limitations of classification schemes for brain tumors based solely on morphology have stimulated searches for molecular markers of nosologic and prognostic value. Gangliosides are logical candidates because there are high concentrations of them in the nervous system, there is evidence of their roles in regulation of growth and differentiation, and data from small series suggest correlations between ganglioside composition and glioma type. METHODS: Ganglioside compositions were determined for 70 primary human brain tumors: 16 low grade astrocytomas (LG), 12 anaplastic astrocytomas (AA), 34 glioblastoma multiformes (GBM), and 8 primitive neuroectodermal tumors (PNET). This method involved identification and quantitation of specific gangliosides using chemical analysis and immunoanalysis. RESULTS: Among all tumor types, histologic grade correlated with a progressive loss of 1b gangliosides (P < 0.0001). GQ1b was higher in LGs than in AAs (P < 0.001). Both GT1b and GD1b were higher in AAs than GBMs (P < 0.01 and 0.05, respectively) and lower in PNETs than in GBMs (P < 0.05). GM3 was higher in PNETs than in any astrocytoma group and higher in GBMs than in either AAs or LGs. There was a significant difference in the content of 3'-LM1 among all groups (P < 0.005), between AAs and GBMs (P < 0.05), and between low grade ordinary and juvenile pilocytic astrocyomas (P < 0.01). The lacto-series ganglioside 3'-isoLM1 was present in all groups except PNET. CONCLUSIONS: These results indicate that patterns of gangliosides could be of considerable value in refining the classification and diagnosis of primary human brain tumors.

Adult↗

PubMed1994

Prognostic significance of flow cytometry deoxyribonucleic acid analysis of human astrocytomas.

Flow cytometry was used to determine the deoxyribonucleic acid ploidy and proliferative activity of 230 astrocytomas. The relationships among survival, ploidy, proliferation, histological features, and clinical variables were analyzed. Multivariate analysis confirmed the independent prognostic significance of the S-phase fraction (P < 0.01), ploidy (P = 0.04), age at diagnosis (P < 0.001), extent of surgery (P < 0.01), and sex (P = 0.03). Three groups with significantly different survival were defined based on S-phase fraction ranges of < 3%, 3%-5.9%, and > or = 6%. The strong correlation between the S-phase fraction and survival confirmed the importance of quantitative proliferation assays in predicting tumor behavior and demonstrated that specific reference ranges can be defined for clinical application. The weaker association between ploidy and survival leaves the usefulness of the determination of ploidy with flow cytometry in doubt.

Adolescent↗

PubMed1994

Prognostic significance of flow cytometry deoxyribonucleic acid analysis of human oligodendrogliomas.

Flow cytometry was used to determine the deoxyribonucleic acid ploidy and proliferative activity of 60 oligodendrogliomas and oligoastrocytomas. The relationships among survival, ploidy, proliferation, histological features, and clinical variables were analyzed. Survival was strongly associated with the S-phase fraction (P < 0.001). Three groups with significantly different survival rates were defined, based on S-phase fraction ranges of < 3%, 3 to 5.9%, and > 6%. Significant associations between survival and age at diagnosis (P < 0.001), tumor grade (P < 0.001), and extent of surgery (P < 0.01) were found also. 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 flow cytometry-determined S-phase fraction in this regard and demonstrated that specific reference ranges could be defined for clinical application. In contrast, the determination of ploidy by flow cytometry was not useful in the evaluation of oligodendrogliomas.

Adolescent↗

PubMed1993

Expression of the tumor suppressor gene DCC in human gliomas.

Reduced expression and/or allelic loss of the putative tumor suppressor gene DCC has been demonstrated in colorectal, gastric, pancreatic, esophageal, breast, and hematological malignancies. We examined the expression of the DCC gene in 22 tissue samples from human gliomas (glioblastoma multiforme, oligodendroglioma, and mixed oligodendroglioma/astrocytoma). Seven of 8 glioblastomas multiforme (88%) had reduced or absent DCC expression, and 8 of the other 14 tumors underexpressed DCC when compared to normal brain tissue. These results demonstrate that reduced expression of DCC occurs in human malignant gliomas and may be part of a common genetic pathway leading to neoplastic transformation and/or tumor progression.

Adult↗

PubMed1993

Regional heterogeneity in the DNA content of human gliomas.

BACKGROUND: Regional heterogeneity causes significant errors in the histologic classification and grading of gliomas, but little is known about its implications for other modalities. Attempts to predict glioma behavior using flow cytometry (FCM) have yielded contradictory results, possibly due to regional heterogeneity in DNA content, a recognized phenomenon that has not been evaluated systematically. METHODS: The authors used FCM to analyze the DNA content of 353 regions from 18 resected human gliomas. Five to 60 regions were sampled from each tumor, and the topographic relationships of ploidy, proliferative activity (S-phase fraction [SPF]), and histologic features were established. RESULTS: Most tumors demonstrated heterogeneity among regions in the number and relative sizes of aneuploid populations and/or proliferative activity. The degree of heterogeneity increased with tumor grade. Heterogeneity in histologic features, ploidy, and proliferative activity appeared to vary independently, except for a significant association between the presence of mitotic figures and the SPF of individual regions (P < 0.0001). The clustering of regions with similar percentages of aneuploid cells supported the concept of local clonal expansion. CONCLUSIONS: Gliomas express significant regional heterogeneity in ploidy and proliferative activity and this will have an adverse effect on the usefulness of their analysis. However, the independent variation of ploidy, proliferative activity, and histologic features suggests that the use of multiple analyses may allow more accurate prediction of glioma patient survival. Regional heterogeneity appears be a fundamental property of malignant gliomas; systematic studies to determine its effects on the diagnostic usefulness of other new methods used to evaluate gliomas are indicated.

Aneuploidy↗

PubMed1993

Tumorigenic, invasive, karyotypic, and immunocytochemical characteristics of clonal cell lines derived from a spontaneous canine anaplastic astrocytoma.

Tumor cells from a spontaneously arising canine astrocytoma were isolated and cloned. Three clonally derived cell lines (DL3580 clone 1, DL3580 clone 2, and DL3580 clone 3) were developed and found to express glial fibrillary acidic protein (GFAP) as well as epidermal growth factor receptor (EGFR/c-erbB1). The cell lines were tumorigenic as subcutaneous xenografts or as intracranial implants in athymic mice, or both. Both the monolayer astrocytoma cells and the xenograft tumor cells from clone 2 were aneuploid, with a modal number of 84 chromosomes per metaphase; clones 1 and 3 were also aneuploid with modal numbers of 82 and 75/79, respectively. The histology of both the initial spontaneously occurring tumor in the dog and the intracranial astrocytoma in athymic mice demonstrated features of diffuse infiltration into normal brain. These newly developed canine glioma cell lines are karyotypically stable for 1 yr in culture and carry the same marker chromosomes as the parental lines. These glioma cell lines may serve as models for investigating mechanisms of glioma invasion into brain. Additionally, clonal cell lines with divergent properties isolated from the same tumor may assist in studies of the molecular basis of astrocytoma progression and heterogeneity.

Animals↗

PubMed1993

Regional heterogeneity in the proliferative activity of human gliomas as measured by the Ki-67 labeling index.

The effects of regional heterogeneity on the accuracy of histological grading of gliomas are well known, but little has been reported about its implications for other diagnostic modalities. This study investigated the relationships of regional heterogeneity in tumor proliferative activity, measured by Ki-67 labeling indices (LI), and histological grades for 16 regionally sampled glioma resections. There was a strong correlation between histological grades and Ki-67 LI in individual regions (p < 0.001), and both methods demonstrated comparable heterogeneity. Heterogeneity increased with tumor grade, probably as an expression of the increased genetic instability that accompanies tumor progression. Similarly, regions with comparable proliferative activity tended to cluster, paralleling clonal expansion. Thus, both histological grading and Ki-67 LI are subject to heterogeneity-induced sampling errors that limit their diagnostic accuracy, particularly in small biopsies. However, fewer grading errors occurred when using both methods together than when using either method alone, suggesting that the use of multiple techniques may reduce the adverse effects of regional heterogeneity on diagnostic accuracy. Regional heterogeneity appears to be a ubiquitous feature of gliomas: it also has been reported in karyotype, p53 oncogene mutations, and PDGF and EGFR expression. The effects of regional heterogeneity on new methods for studying gliomas need to be considered.

Brain Neoplasms↗

PubMed1992

Flow cytometric analysis of deoxyribonucleic acid ploidy and proliferation in choroid plexus tumors.

The deoxyribonucleic acid (DNA) content of 10 choroid plexus tumors, including 4 malignant tumors and 3 normal choroid plexus controls, was analyzed by flow cytometry to determine whether a ploidy or proliferation rate is a better predictor of tumor behavior than histological features. Nine of 10 neoplasms had both diploid and aneuploid modal populations. One neoplasm and all three control cases had only a diploid peak. Among the tumors, the DNA indices of the aneuploid peaks ranged from 1.1 to 2.2. The percentage of aneuploid cells ranged from 7 to 99, and no distinction was made between benign and malignant. Proliferation rates were estimated from the combined S-phase fractions (SPF). The mean SPF of the control group was 0.7% +/- 0.15% SD. The mean SPF of the benign tumors (1.1 +/- 0.82% SD) was significantly different from the malignant group (7.0 +/- 1.25% SD; range, 5.3 to 8.6%) P = 0.0095. Low SPF fractions always correlated with favorable outcome. Higher proliferation rates were generally associated with an aggressive course. Evaluation of proliferation rates may help predict the behavior of choroid plexus tumors, particularly when histological features are equivocal. Measurement of DNA ploidy does not appear to have a role in the evaluation of choroid plexus tumors.

Adolescent↗

PubMed1990

Neonatal intracranial teratomas.

Two neonates with intracranial teratomas presented with cranial enlargements a few weeks after birth. Both cases underwent surgery: one died intraoperatively; the other is the longest known survivor, alive 7 years and 9 months after subtotal excision of a mature teratoma of the left sylvian fissure. Previous operations have been relatively few and nearly all have been unsuccessful. Size and favorable location may be the most important prognostic features regardless of the histologic classification as mature or immature. One of our cases demonstrates that even subtotal excision of a mature teratoma can result in long-term survival.

Brain Neoplasms↗

PubMed1990

Gliomas: classification with MR imaging.

The findings at magnetic resonance (MR) imaging in a group of 36 pathologically verified supratentorial gliomas were analyzed and compared with the biopsy diagnoses (a) to determine whether MR imaging could be used to classify astrocytic-series tumors into a three-tiered system of low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme; and (b) to evaluate MR imaging features that may aid in this classification. The MR characteristics evaluated were crossing of the midline, edema, tumor signal heterogeneity, hemorrhage, border definition, cyst formation or necrosis, and mass effect. The statistically significant MR characteristics (positive predictors) were mass effect (P = .0000) and cyst formation or necrosis (P = .0512). The MR accuracy rate approached that of neuropathologic diagnosis, which is subject to sampling errors. MR imaging may serve as an adjunct in case management when the clinical course and MR findings appear to be at odds with the neuropathologic diagnosis.

Anaplasia↗

PubMed1989

Brachial plexus meningioma, report of a case with immunohistochemical and ultrastructural examination.

Peripheral nerve meningiomas are exceedingly rare neoplasms of controversial origin; only four cases have been reported. Proposed origins of ectopic meningiomas include extradural trapping of arachnoid cells during embryogenesis, ectopic migration of arachnoid cell nests with the developing peripheral nerve, and metaplasia of mature peripheral nerve sheath cells or a common progenitor cell. In this report of a meningioma of the brachial plexus, immunohistochemical and ultrastructural examinations of the tumor matched all the criteria of a traditional meningioma but failed to clarify the origins of such neoplasms.

Brachial Plexus↗