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Biomedical subjects

J N Bruce

Publications and source records attributed to J N Bruce.

At least 37 records · Page 2Linked to original sources
PubMed1998

Disparity in expression of protein kinase C alpha in human glioma versus glioma-derived primary cell lines: therapeutic implications.

Intracellular signal transduction by the protein kinase C (PKC) family of enzymes plays a critical role in carcinogenesis and cellular growth regulation. Recent studies have suggested that the PKC isoform alpha may be a critical target for antiglioma therapy in humans (G. H. Baltuch et al., Can. J. Neurol. Sci., 22: 264-271, 1995). We studied the expression and subcellular distribution of the PKC alpha isoform in human high- and low-grade gliomas and also in glioma-derived cell lines with immunoblot analyses. Cell lines derived from high-grade gliomas expressed higher levels of PKC alpha than did cell lines derived from low-grade gliomas. In glioblastoma-derived cell lines, PKC alpha was mainly expressed in the soluble (cytosolic) fraction, indicating an inactive state of the enzyme. When analyzed in freshly frozen samples from human gliomas, the expression of PKC alpha was at similar levels in high- and low-grade tumors and was also similar to the levels in normal brain tissue controls. The PKC partial antagonist bryostatin 1, currently undergoing Phase II testing in patients with malignant gliomas, was capable of specifically down-regulating PKC alpha in vitro in glioblastoma-derived cell lines. However, this was not associated with significant growth inhibition. We conclude that the observed overexpression of PKC alpha in glioblastoma-derived cell lines may be an artifact of in vitro growth. Furthermore, we conclude that expression of PKC alpha in glioma-derived cell lines is not essential for cellular growth in vitro because down-regulation of PKC alpha following treatment with bryostatin 1 was not associated with growth inhibition.

Antineoplastic Agents↗
PubMed1997

Somatic mutations of PTEN in glioblastoma multiforme.

Alterations of the PTEN gene occur in glioblastoma multiforme. To determine the frequency of PTEN alteration, 34 consecutive glioblastomas were studied in detail. Sequencing each of the nine exons amplified from tumor DNA revealed 11 mutations. Analysis of polymorphic markers within and surrounding the PTEN gene identified an additional four homozygous deletion mutations. Loss of heterozygosity (LOH) was observed in 25 of 34 (74%) cases. All mutations occurred in the presence of LOH. PTEN was mutated in 44% (15 of 34) of all glioblastomas studied and 60% (15 of 25) of tumors with LOH on 10q. Thus, PTEN appears to be the major target of inactivation on chromosome 10q in glioblastoma multiforme.

Astrocytoma↗
PubMed1997

Eosinophilic granuloma of the clivus: case report, follow-up of two previously reported cases, and review of the literature on cranial base eosinophilic granuloma.

OBJECTIVE AND IMPORTANCE: To our knowledge, this is the first reported case of the use of stereotactic radiotherapy for an eosinophilic granuloma (EG) of the clivus. We report follow-up information on two previously reported cases and suggest a management plan for this rare lesion. CLINICAL PRESENTATION: We report the case of a 4.5-year-old boy who presented with a complete abducens palsy on the right with an associated head turn. A computed tomographic scan of his head revealed a lytic lesion on that side, and magnetic resonance imaging showed the mass to be of low intensity on T1-weighted images and of high intensity on T2-weighted images with heterogeneous enhancement. INTERVENTION: A transnasal stereotactic biopsy was performed, revealing an EG. The patient was treated with stereotactic radiotherapy, and he became symptom-free with radiographic resolution of his lesion. Reviewing the literature, we found 13 series with 87 cases of EG in the petrous portion of the temporal bone. EG in the cranial base occurring outside of the temporal bone or in the temporal bone and extending intracranially is, however, quite rare, with only nine other cases reported, two of them clival. CONCLUSION: These findings suggest a classification schema in which cranial base EG lesions be grouped with either the more common extracranial petrous temporal bone lesions or the very rare intracranial lesions. Although there are few cases in the literature, treatment results indicate that clival EG, and perhaps all intracranial cranial base EGs, be treated by a biopsy alone, followed by surgery or stereotactic radiotherapy if there is an incomplete resolution of the symptoms or if there is a recurrence.

Child, Preschool↗
PubMed1996

Dural closure with laser tissue welding.

This study investigates the use of tissue-soldering techniques to substitute or reinforce traditional suture closure of dural incisions. Fresh human cadaveric dura was incised and subsequently closed by use of three techniques: (1) conventional interrupted suture with 4-0 silk (n = 25), (2) laser solder reinforced suture closure (n = 25), and (3) laser solder closure alone (n = 25). Anastomosis tensile strength and hydrostatic leak pressures were measured. Dural repair was also performed in 15 live Lewis rats. Dural closure was accomplished with 9-0 Prolene sutures (n = 5), laser-reinforced suture closure (n = 5), and laser solder closure alone (n = 5). Histologic examination of the closure immediately after soldering and 2 weeks later was performed. Suture closure alone had the lowest leak pressure, 9.4 +/- 1.7 mm Hg, and an intermediate break point, 13.3 +/- 2.1 Kgf/cm2. Measurements with laser solder alone revealed a mean leak pressure of 26.2 +/- 3.7 mm Hg and a break point of 4.6 +/- 1.4 Kgf/cm2. Solder-reinforced suture closure leak pressure measured 64.0 +/- 6.7 mm Hg and 21.4 +/- 2.4 Kgf/cm2. There was a statistically significant increase in leak pressure and tensile strength in the closures performed with laser weld reinforcement of traditional suture technique (p = 0.0001). Dural closure with laser tissue welding alone provided an immediate leak-free closure, but with poor tensile strength. Histologic examination of welded dura and underlying brain tissue showed no evidence of thermal injury in four of five animals studied. Laser welding may significantly decrease the incidence of cerebrospinal fluid leak after dural closure. In addition, laser tissue welding also makes dural closure possible where space constraints make traditional suture closure difficult.

Animals↗
PubMed1996

Frequent type 2 neurofibromatosis gene transcript mutations in sporadic intramedullary spinal cord ependymomas.

OBJECTIVE: To further investigate the role of Type 2 neurofibromatosis (NF2) gene transcript mutations in the sporadically occurring counterparts of NF2-associated tumors. METHODS: Reverse transcription-polymerase chain reaction followed by agarose gel electrophoresis, single strand conformation polymorphism analysis, and automated deoxyribonucleic acid sequence analysis were used to screen for mutations in the NF2 gene transcript in seven unrelated patients with sporadic intramedullary spinal cord ependymomas. RESULTS: Five of seven intramedullary spinal cord ependymomas harbored detectable mutations. All of these mutations occurred in the region of the transcript that is homologous to known cytoskeletal proteins and resulted in significant truncation of the predicted protein product. CONCLUSION: Mutations of the NF2 transcript occur in the majority of sporadic intramedullary spinal cord ependymomas. These mutations are frequent in a region of the transcript that is homologous to a family of cytoskeletal proteins, and they probably render the protein product inactive. These results add to the body of knowledge concerning the role of the NF2 gene transcript in tumorigenesis.

Adult↗
PubMed1996

Inhibition of the growth of glioblastomas by CGP 41251, an inhibitor of protein kinase C, and by a phorbol ester tumor promoter.

Protein kinase C (PKC) plays a central role in signal transduction pathways that mediate the action of certain growth factors, tumor promoters, and cellular oncogenes. To explore whether PKC might be an appropriate target for the chemotherapy of human brain tumors, cell lines were established from five glioblastomas, one mixed gliosarcoma and glioblastoma, two astrocytomas, and one choroid plexus carcinoma. The staurosporine derivative CGP 41251, an inhibitor of PKC, inhibited cell proliferation in all nine cell lines with an IC50 in the range of 0.4 micrometer. Drug withdrawal and clonogenicity assays showed that CGP 41251 induced an irreversible growth arrest. Three cell lines were examined in detail: two human glioblastoma cell lines, GB-1 and GB-2, and one gliosarcoma cell line, GS-1. All of these three cell lines were highly aneuploid and displayed morphologies and immunohistochemical markers characteristic of the glial lineage. The compound 12-O-tetradecanoylphorbol-13-acetate (TPA), a tumor promoter and activator of PKC, also inhibited the growth of these cell lines. CGP 41251 in combination with TPA caused further growth inhibition. Cultures treated with CGP 41251 displayed an increase in the fraction of cells in G2-M, a decrease of cells in S phase, and no consistent effect on G0-G1. Immunohistochemical analyses demonstrated that growth inhibition by CGP 41251 was associated with the formation of giant nuclei with extensive fragmentation and apoptotic bodies. These effects of CGP 41251 were abrogated by withdrawal of serum from the medium or by exposure of these cells to aphidicolin, actinomycin D, cycloheximide, or TPA. In contrast to the effects seen with the glioblastoma cell lines, nontransformed astrocyte lines remained viable in the presence of 0.4 and 0.8 micrometer CGP 41251 and displayed only a slight increase in the fraction of giant nuclei with fragmentation. The antitumor activity of CGP 41251 was demonstrated in vivo against xenografts of the glioblastoma cell lines U87 MG and U373 MG. These findings suggest that CGP 41251 might be a useful agent for the treatment of glioblastomas.

Aged↗
PubMed1995

Surgical management of pineal region tumors.

The authors advocate an aggressive surgical approach to pineal region tumors to provide a definitive histological diagnosis and to facilitate extensive tumor removal. This strategy is based on their surgical experience in 160 operations for pineal region tumors in which operative mortality was 4% with 3% permanent major morbidity. One-third of pineal tumors were benign for which surgery alone was usually curative. A gross total removal was possible in 31 of 107 malignant tumors. The supracerebellar infratentorial approach was preferred in 86% of patients. The tumors displayed considerable histological diversity with germ cell tumors most common (37%), followed by glial cell tumors (28%) and pineal cell tumors (23%). Mixed tumors occurred 15% of the time. Spinal metastases were rare, occurring in less than 10% of patients with malignant tumors. These results with a large series of pineal region tumors demonstrate the safety and efficacy of aggressive pineal tumor surgery.

Adolescent↗
PubMed1995

Trends in incidence of primary malignant brain tumors in USA, 1981-1990.

BACKGROUND: There has been considerable controversy regarding whether a recent observed rise in brain tumor incidence is real and so suggestive of increasing exposure to environmental carcinogens, or whether it is largely explainable by changes in diagnostic technology, particularly the introduction of computerized axial tomography (CT) scans in the 1970s. We analysed data from the US Surveillance, Epidemiology, and End Results (SEER) Program to investigate whether there was a rise of brain tumor incidence during 1981-1990, the period after CT scans became extensively available, and if so, the rates of which specific histologic subtypes have risen. METHODS: Age- and sex-specific, as well as age-adjusted incidence rates were calculated for each brain tumor histologic subtype. Regression analysis was used to estimate age-adjusted incidence rate ratios (RR) for different periods and to examine time trends. RESULTS: For all histologic subtypes, the incidence rates increased with age. Regarding time trends, lymphomas in men increased in all age groups during the study period with the age-adjusted rate ratio reaching 5.6 (95% CI: 3.7-8.3) for 1989-1990 as compared to 1981-1982. Lymphoma in women and glioblastoma multiforme in both sexes also appear to have increased, particularly in the elderly. Other histologies did not show any time trends in the age-specific or age-adjusted analyses. CONCLUSION: Our histology-specific analysis is not suggestive of any significant increase in the incidence of brain tumors during 1980-1990, except for lymphomas in men.

Adult↗
PubMed1995

Differential diagnosis in cushing syndrome. Use of corticotropin-releasing hormone.

Testing with ovine corticotropin-releasing hormone (CRH) has facilitated the differential diagnosis of Cushing syndrome, which is often not straightforward. We provide our experience between January 1989 and August 1993 with 30 patients with Cushing syndrome and describe 4 cases in detail to illustrate how CRH testing can be successfully applied to some of the difficulties encountered in the evaluation. CRH testing proved to be particularly useful in distinguishing cases of Cushing syndrome of adrenal etiology from those of Cushing disease with low or undetectable adrenocorticotropin (ACTH) levels. CRH testing during petrosal sinus sampling was also found to help distinguish the ectopic ACTH syndrome from pituitary-dependent Cushing syndrome. Our cases illustrate the need for careful biochemical evaluation before proceeding to imaging studies. Using CRH testing to evaluate cases of Cushing syndrome in which standard testing was inconclusive can provide useful information and lead to a more rapid determination of etiology and definitive therapy than previously possible.

ACTH Syndrome, Ectopic↗
PubMed1995

Association of malignant brain tumors and cancers of other sites.

PURPOSE: We conducted an exploratory study of brain tumors that occurred as a second primary malignancy to identify potential risk factors for brain tumors. METHODS: Using data from the Surveillance, Epidemiology, and End Results (SEER) Program, we calculated the sex-specific standardized incidence ratio (SIR), adjusted to age and time period, as an estimate of the relative risk (RR) of developing a second primary brain tumor following other cancers. RESULTS: We found an elevated RR of brain tumors after bladder cancer in both men (RR, 1.7; 95% confidence interval [CI], 1.2 to 2.3) and women (RR, 1.7; 95% CI, 0.8 to 3.2); this effect was present for both astrocytoma and glioblastoma multiforme. Elevated RRs of brain tumors were also found after sarcoma (RR, 4.4; 95% CI, 1.8 to 9.0) and leukemia (RR, 2.9; 95% CI, 1.6 to 4.8) in men, and after colorectal cancer (RR, 1.8; 95% CI, 1.3 to 2.4) and endometrial cancer (RR, 1.4; 95% CI, 1.0 to 1.9) in women. The highest RR observed in this study was for CNS lymphoma following any first primary malignancy in men (RR, 7.9; 95% CI, 5.5 to 11.0). CONCLUSION: The associations of brain tumors with bladder, colorectal, and endometrial cancers in women, and an increased occurrence of CNS lymphoma as a second malignancy in men, are new findings that have not been described previously.

Adult↗
PubMed1991

Non-neoplastic pineal cysts.

We identified 53 patients with non-neoplastic cysts of the pineal gland. In contrast to patients with pineal neoplasms, pineal cysts are usually asymptomatic. They infrequently obstruct the aqueduct to cause hydrocephalus or compress the tectum to produce the neuro-ophthalmologic signs of dorsal midbrain dysfunction. Obstructive hydrocephalus was present in only five patients (9.4%); three of them showed clinical signs of Parinaud's syndrome. CT and MRI typically reveal a cystic mass that averages 1.6 cm in anteroposterior (A-P) diameter with calcification at the periphery and faint rim-like contrast enhancement. Sagittal MRI is the most useful diagnostic test because it shows the anatomic relationship of the cyst to the aqueduct. The mass may compress the tectum and distort the proximal aqueduct; occasionally a large cyst may occlude the aqueduct. All patients with obstructive hydrocephalus had cysts greater than 2.0 cm in A-P diameter. Nine patients had suboccipital craniotomy. In all of them, the cysts contained clear fluid and were easily removed. We advocate conservative management with clinical observation of these benign lesions that may be developmental variants of normal pineal gland.

Adolescent↗
PubMed1990

Expression and modulation by cytokines of the intercellular adhesion molecule-1 (ICAM-1) in human central nervous system tumor cell cultures.

The intercellular adhesion molecule (ICAM-1) has been shown to be important in interactions involving cells of the immune system and to be upregulated in a number of cell culture systems by cytokines, including immune interferon (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha). In the present study, we have determined by fluorescence-activated cell sorter (FACS) analysis and the anti-ICAM-1 monoclonal antibody (MAb) CL203.4 the base-line expression of ICAM-1 and its modulation by recombinant IFN-beta, IFN-gamma and TNF-alpha in early passage (less than 15) human central nervous system (CNS) tumor-derived cell cultures. These cultures were established from various malignancies, including glioblastoma multiforme (GBM), astrocytoma (AST), ganglioglioma, medulloblastoma, meningioma and a pineal tumor. ICAM-1 expression was highest in the GBM- and AST-derived cell cultures and was lowest in the ganglioglioma and normal pineal cell cultures. Variable ICAM-1 expression was found, however, in tumors of the same histological group. In several cell cultures the variable expression observed by FACS was substantiated by the intensity of the molecular species immunoprecipitated by the anti-ICAM-1 MAb CL203.4 from these cells. All the cell cultures displayed variable but consistent increases in ICAM-1 expression following treatment with IFN-gamma or TNF-alpha. In general, the degree of increase in ICAM-1 expression was greatest in cultures exposed to TNF-alpha. Upregulation of ICAM-1 expression in an established glioblastoma multiforme cell line was of greater magnitude and more rapid following TNF-alpha treatment (within 2 to 3 hr) than exposure to IFN-gamma (by 24 hr). In several cultures, IFN-beta also increased ICAM-1 expression and enhanced the increase induced by TNF-alpha. The results of the present study indicate that variable expression of ICAM-1 is a common property of early passage cultures of CNS tumors and recombinant interferons and TNF-alpha can differentially upregulate ICAM-1 expression in these CNS tumor cell cultures.

Antibodies, Monoclonal↗
PubMed1990

Pineal tumors.

Pineal-region tumors constitute a diverse group of tumors. We recommend an aggressive surgical approach to these tumors for diagnostic as well as therapeutic purposes. Approximately one third of all pineal tumors are benign, resectable lesions and surgical therapy provides the best opportunity for a cure. Debulking procedures are beneficial in patients with malignant tumors both surgically and because they provide tissue specimens for diagnostic purposes to properly direct postoperative adjuvant therapy. Surgical results have been excellent, with an overall mortality and morbidity rate of 12 per cent and virtually no permanent deficits in patients with benign tumors.

Adolescent↗
PubMed1987

Vascular permeability induced by protein product of malignant brain tumors: inhibition by dexamethasone.

Serum-free conditioned medium derived from confluent monolayer cultures of malignant human astroglial tumors contains a substance that rapidly increases capillary vascular permeability after intradermal injection into guinea pigs. Accumulation of vascular permeability factor (VPF) activity occurs with increasing duration of tumor incubation in vitro. Expression of this activity is inhibited by incubation of cell cultures with cycloheximide or dexamethasone. This VPF is an acid-stable heat-labile macromolecule that is inactivated by trypsin and pepsin and binds immobilized heparin. Activity is retained by ultrafiltration with 30,000-dalton cut-off microconcentrators. Pretreatment of test animals with systemic dexamethasone prior to intradermal injection of VPF diminishes microvascular permeability. Furthermore, VPF activity is not inhibited by antihistamines. Secretion of VPF may cause the vasogenic brain edema that is frequently associated with malignant primary and metastatic intracerebral tumors. Inhibition by dexamethasone of both VPF expression in tissue culture, and VPF activity at the microvascular level in test animals, is in keeping with the known efficacy of this agent in treating the vasogenic edema associated with brain tumors.

Animals↗