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Biomedical subjects

G H Barnett

Publications and source records attributed to G H Barnett.

At least 19 recordsLinked to original sources
PubMed2003

Rapid detection of allelic losses in brain tumours using microsatellite repeat markers and high-performance liquid chromatography.

High-performance liquid chromatography (HPLC) is a recently introduced high-capacity automated method for detecting unknown mutations (denaturing HPLC) or for sizing DNA fragments under nondenaturing conditions. We have adapted the HPLC method for detection of loss of heterozygosity (LOH) and used glial tumours as a model to evaluate its sensitivity and specificity in comparison to conventional denaturing polyacrylamide gel electrophoresis. A total of 20 oligodendrogliomas (grades II and III), and five astrocytic tumours (grades III and IV) were analysed using 14 polymorphic microsatellite markers mapping to regions on chromosomes 1p, 19q, and 10q using both DNA-HPLC and denaturing gel electrophoresis. This study demonstrated complete concordance between both methods. However, unlike gel electrophoresis, HPLC is automated, does not require post-PCR processing, and does not require hazardous radioactive or expensive fluorescent labelling. Our data suggest that HPLC is a reliable and sensitive method for detection of allelic losses in tumour samples and it is a favourable alternative for high-sensitivity LOH detection in both research and diagnostic environments.

Brain Neoplasms↗
PubMed2003

Genetic vulnerability following traumatic brain injury: the role of apolipoprotein E.

Apolipoprotein E (APOE) is thought to be responsible for the transportation of lipids within the brain, maintaining structural integrity of the microtubule within the neurone, and assisting with neural transmission. Possession of the APOE epsilon4 allele has also been shown to influence neuropathological findings in patients who die from traumatic brain injury, including the accumulation of amyloid beta protein. Previous clinical studies reporting varying outcome severities of traumatic brain injury, including cognitive and functional recovery, all support the notion that APOE epsilon4 allele possession is associated with an unfavourable outcome. Evidence from experimental and clinical brain injury studies confirms that APOE plays an important role in the response of the brain to injury.

Alleles↗
PubMed2001

Epidermal growth factor regulates astrocyte expression of the interleukin-4 receptor via a MAPK-independent pathway.

Human astrocytes express the interleukin (IL)-4 receptor alpha chain (IL-4R alpha) in vitro and in vivo but mechanisms governing astrocyte IL-4R alpha expression have not been established. We hypothesized that epidermal growth factor (EGF) and IL-4, agents that profoundly affect astrocyte proliferation, might also alter IL-4R alpha expression. Exposure to EGF for 24 h enhanced IL-4R alpha mRNA levels; in contrast, IL-4 yielded no increase. Immunoblotting demonstrated that EGF but not IL-4 increased astrocyte IL-4R alpha protein after 2--4 days of exposure. Similarly, EGF but not IL-4 strongly activated phosphorylation of p42/p44 extracellular regulated kinase isoforms, a reaction blocked by the mitogen-activated protein kinase (MAPK) inhibitor, PD98059. PD98059 also blocked EGF-stimulated DNA synthesis but not IL-4R alpha mRNA levels, while antibody to the EGF receptor (erbB1) blocked both EGF effects. Data suggest that astrocyte IL-4R alpha expression is upregulated by EGF but not by IL-4 in an EGF-receptor-dependent manner and that mechanisms are independent of MAPK activation.

Astrocytes↗
PubMed2001

Tumor distribution and survival in six patients with brain metastases from cervical carcinoma.

OBJECTIVE: The aim of this study was to investigate the patterns of brain involvement and the outcome of patients with brain metastases from cervical carcinoma. METHODS: Between January 1982 and November 1999, 1279 patients with brain metastases were treated at the Cleveland Clinic. Six of them had brain metastases from cervical carcinoma. We retrospectively reviewed the patient and tumor characteristics at the time of the primary diagnosis as well as at the time of the brain metastases diagnosis. RESULTS: Brain metastases from cervical carcinoma were rarely accompanied by systemic disease, but they were commonly accompanied by uncontrolled local-regional disease. The median interval from the appearance of the primary carcinoma to the detection of brain metastases in 5 patients was 12 months. Multiple brain lesions developed in 4 of 6 patients and consisted of multiple tumors distributed in the cerebral hemispheres (2 patients) or both the cerebral and the cerebellar hemispheres (2 patients). Only 2 patients had a single lesion confined to a cerebral hemisphere. One patient was treated with stereotactic radiosurgery alone, 3 with surgery followed by whole brain radiation therapy, 1 with whole brain radiotherapy, and 1 each with whole brain radiotherapy and stereotactic radiosurgery. Patients treated with surgery had a median survival of 8.25 months, while patients treated with whole brain radiotherapy with or without stereotactic radiosurgery had a median survival of 3.75 months. The 1 patient treated with stereotactic radiosurgery alone survived for 22.5 months. CONCLUSION: Although the number of the patients was too small to detect definitive patterns of brain metastases from cervical carcinoma, the results of our review suggest that, in contrast to previous reports, extended survival can occur with more aggressive treatment such as surgery or stereotactic radiosurgery.

Adult↗
PubMed2001

The effect of radiation therapy on brain metastases from endometrial carcinoma: a retrospective study.

OBJECTIVE: The objective of this study was to investigate the effectiveness of radiation therapy as a treatment for brain metastases from endometrial carcinoma. METHODS: Between July 1985 and November 1999, 10 patients with brain metastases from endometrial carcinoma were treated at the Cleveland Clinic. We reviewed the patient and tumor characteristics at the time of the primary diagnosis and the brain metastases diagnosis. For the 8 patients who received radiation therapy with or without surgery, we analyzed the treatment results with regard to survival and local control of the metastases. RESULTS: Brain metastases from endometrial carcinoma were commonly accompanied by uncontrolled local-regional disease and systemic metastases. Multiple brain lesions developed in 7 of 10 patients. Two patients were treated with surgery alone and had a median survival of 2.75 months (4 and 1.5 months) after the brain metastases diagnosis. Three patients were treated with surgery and radiation therapy and lived for a median survival of 15 months (range 11.5 to 15.5 months). The 5 patients who were treated with radiation therapy without surgery had a median survival of 2.4 months (range 0.25 to 6 months). Patients with multiple brain metastases had a shorter survival than patients with a single metastasis. CONCLUSION: Overall survival after brain metastases development in patients with endometrial carcinoma was poor. Although the number of patients was small, radiation therapy alone resulted in poor survival. Combination treatment with surgery and radiation therapy may improve survival for selected patients.

Adenocarcinoma↗
PubMed2001

Metastatic seeding of the stereotactic biopsy tract in glioblastoma multiforme: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: The first case was recently reported of tumor seeding by glioblastoma multiforme (GBM) after stereotactic biopsy. This occurred despite radiosurgical treatment of the lesion post-biopsy. We report the first case of metastatic seeding along the needle biopsy tract of a GBM in which the tract was within the treatment field of subsequent fractionated radiation therapy. CLINICAL PRESENTATION: A 56-year-old man presented with left-sided focal motor seizures. An MRI showed an enhancing right cingulate gyrus lesion. INTERVENTION: A stereotactic biopsy of the lesion disclosed GBM. Radiation therapy was begun 25 days after biopsy and was completed 39 days thereafter. The biopsy tract received a minimum of 60 Gy. Subsequent magnetic resonance scanning showed the lesion to have doubled in size and evidence of enhancement along the biopsy tract. At surgery, specimens obtained from the biopsy tract, as determined using surgical navigation, revealed GBM. CONCLUSION: Seeding of the biopsy tract, radioresistance and the time interval until radiotherapy are the most likely explanations for tumor growth along the biopsy tract in this case. Consideration should be given for an early start to radiotherapy among those who undergo stereotactic biopsy for GBM. Further research will allow one to determine the radiosensitivity of these tumors and determine which patients may benefit from a radiosurgical or fractionated radiotherapy boost to the biopsy tract.

Antineoplastic Agents, Hormonal↗
PubMed2001

Clinical and economic consequences of early discharge of patients following supratentorial stereotactic brain biopsy.

OBJECT: The goal of this study was to determine the clinical and economic consequences of early discharge (< 8 hours) of patients following stereotactic brain biopsy (SBB). METHODS: The records of all patients who underwent percutaneous SBB at The Cleveland Clinic Foundation, a tertiary care teaching hospital, during 1994 and 1995 (Group A) were retrospectively reviewed to collect data on the nature and timing of perioperative (< 48 hours) clinical and radiological complications. Biopsies were performed using image-guided stereotaxy either with or without a frame. Based on the results, guidelines for early discharge of patients following SBB were implemented. Information on the nature and timing of perioperative complications was also collected prospectively in all patients who underwent percutaneous SBB from January 1996 through July 1998 (Group B). Hospital financial records for patients who underwent SBB in 1997 and 1998 were also reviewed and assessed for net revenue stratified by discharge status: early discharge (< 8 hours), extended outpatient observation (> or = 8 and < 24 hours). and inpatient hospitalization (> or = 24 hours). In Group A, 130 biopsies were performed. There were five serious complications (3.8%), of which four were transient, and there was one death (0.8%). The death and any sustained deficit occurred in patients in whom a clot had been demonstrated on postoperative CT scans. All complications were detected within 6 hours after surgery. Intraoperative bleeding occurred in 12 patients (9.2%), but was associated with only 40% of cases in which hemorrhage appeared on postoperative CT scans. Guidelines for early discharge (< 8 hours) following SBB were developed and stipulated the absence of the following: 1) intraoperative hemorrhage; 2) new postoperative deficit; and 3) clot on a postoperative CT scan. In Group B, 139 biopsies were performed. There were three serious complications (2.2%), one of which was sustained due to a clot that had been demonstrated on the postoperative CT scan. All complications were detected within 6 hours postsurgery. There were no deaths in this group. Intraoperative bleeding occurred in 11 patients (7.9%), requiring intraoperative craniotomy to control bleeding in one case. Hospital financial records were available for 96 patients, of whom 22 were discharged from the hospital early, 11 were observed for an extended outpatient period, and the remainder were retained for inpatient hospitalization. Average net hospital incomes on technical charges for patients in the inpatient hospitalization, extended outpatient observation, and short-stay (early discharge) groups were $1778, $1175, and $1219, respectively, in 1997, but declined to -$889, -$1339, and $671, respectively, in 1998. The ratios of indirect costs to direct technical costs were 132.5%, 128.7%, and 103.7%, respectively. CONCLUSIONS: Early discharge of patients following SBB of supratentorial lesions is safe in the absence of excessive intraoperative bleeding, new postoperative deficit, and clot on a postoperative CT scan. Extended outpatient observation (8-23 hours) is not clinically necessary and may be economically prohibitive in the setting of a teaching hospital.

Biopsy↗
PubMed2001

Delayed appearance of carbon granulomas of the scalp after use of carbon fiber pins for refixation of a stereotactic head frame. Case report.

The authors present a case involving the formation of several carbon granulomas in the scalp of a woman 7 years after she underwent craniotomy. Her operation had included the use of carbon fiber pins for refixation of a stereotactic head frame. Carbon granulomas have been noted in multiple organs following surgical or traumatic carbon deposition, but have not been reported in association with neurosurgical carbon fiber pins used for head fixation. The lesions in this case arose a few months after initiation of chemotherapy for the patient's brain tumor. The relationship of carbon and cutaneous granuloma formation to adjuvant therapies and treatment strategies is discussed.

Bone Nails↗
PubMed2000

Application of recursive partitioning analysis and evaluation of the use of whole brain radiation among patients treated with stereotactic radiosurgery for newly diagnosed brain metastases.

PURPOSE: To evaluate the usefulness of whole brain radiotherapy (WBRT) and of the Radiation Therapy Oncology Group recursive partitioning analysis (RPA) for brain metastases among patients receiving stereotactic radiosurgery (SRS). METHODS AND MATERIALS: A retrospective analysis was performed on 135 patients who underwent linear accelerator (Linac) (n = 73) or Gamma Knife (n = 62) SRS for newly diagnosed brain metastases at the Cleveland Clinic Foundation between 8/89 and 12/98. Univariate and multivariate analyses were performed to evaluate the effects of age, primary site, control of the primary, interval to development of brain metastases (disease-free interval [DFI]), number of brain metastases, presence of extracranial metastases, Karnofsky performance status (KPS), treatment of brain metastases, and RPA class on overall survival. RESULTS: Application of the RPA classification revealed 29 patients fit the criteria for class I, 96 for class II, and 10 for class III. All of the patients underwent SRS. Fifty-seven patients also received WBRT at the time of initial presentation (SRS and immediate WBRT), and 78 patients received WBRT only if CNS relapse occurred (SRS alone). The median survival for all patients was 7.9 months (range: 1.1-90.1), and was 11.2 months for RPA class I compared to 6. 9 months for RPA classes II-III (p = 0.016). Median survival was 10. 5 months following SRS alone compared to 6.4 months following SRS and WBRT (p = 0.07). On univariate analysis, KPS >/= 80% (p = 0.002) and absence of systemic disease (p = 0.013) were also associated with longer survival, whereas control of the primary, DFI, and number of brain metastases did not have an impact. Multivariate analysis revealed only RPA class (p = 0.023) to be an independent predictor for overall survival, whereas treatment group (p = 0.079) was only marginally significant. At 2 years, immediate WBRT improved control at the original site of metastases (80% vs. 52%, p = 0.03) and prevention of new metastatic sites within the brain, 74% vs. 48% (p = 0.06). The 2-year intracranial disease-free survival was 60% following SRS and WBRT compared to only 34% following SRS alone (p = 0.03). CONCLUSIONS: Despite the inherent biases to select more favorable patients for SRS, the RPA class retains its prognostic value. Omission of WBRT from the initial management was not detrimental in terms of overall survival; however, progressive disease occurred in over 50% of patients treated in this manner. Further studies are required to determine which, if any, patients should be considered for SRS with WBRT held in reserve.

Age Factors↗
PubMed2000

The role of whole brain radiotherapy and stereotactic radiosurgery on brain metastases from renal cell carcinoma.

PURPOSE: We reviewed our experience with patients who have undergone stereotactic radiosurgery (SRS) for brain metastases secondary to renal cell carcinoma (RCC). Analysis was performed to determine the survival, local control, distant brain failure (DBF), and then to define which tumors may not require upfront whole-brain radiotherapy (WBRT). METHODS AND MATERIALS: Twenty-nine patients with 66 tumors underwent SRS from 1991 to 1998. Median follow-up from time of brain metastases diagnoses relative to each tumor was 12.5 months and 6.8 months from the time of SRS. Median SRS dose was 1,800 cGy to the 60% isodose line. Three patients had undergone SRS for previously treated tumors. RESULTS: Median survival time from diagnosis was 10.0 months. Overall survival was not affected by age, addition of WBRT, number of lesions, tumor volume, or the presence of systemic disease. Of the 23 patients with follow-up neuroimaging, 4 of 47 (9%) tumors recurred. The addition of WBRT did not improve local control. Of the 13 patients who presented with a single lesion, 3 went on to develop DBF (23%), while 6 of the 10 patients who presented with multiple metastases developed DBF (60%). CONCLUSION: Patients with brain metastases secondary to RCC treated by SRS alone have excellent local control. The decision of whether or not to add WBRT to SRS should depend on whether the patient has a high likelihood of developing DBF. Our study suggests that patients who present with multiple brain lesions may be more likely to benefit from the addition of WBRT because they appear to be more than twice as likely to develop DBF as compared to patients with a single lesion.

Adult↗
PubMed2000

Results of linear accelerator-based stereotactic radiosurgery for recurrent and newly diagnosed acoustic neuromas.

Stereotactic radiosurgery (SRS) is used to treat acoustic neuromas, but additional information is needed to firmly establish its safety and efficacy. We review our experience over 7 years treating 29 consecutive patients with a modified linear accelerator (linac) SRS system. Between August 1989 and October 1995, 29 patients with a median age of 67 years (range 26 to 83) underwent linac SRS treatment. Twenty-five patients had unilateral acoustic neuromas, and four patients with neurofibromatosis type II had bilateral vestibular schwannoma. Eligibility criteria for SRS were recurrent tumors (n = 9), age >65 (n = 16), or patient preference (n = 6). Follow-up magnetic resonance imaging scans were performed on all patients. The most common presenting symptoms were hearing impairment (18 patients) and gait difficulties (17 patients). Ten patients were deaf in the affected ear prior to treatment. Doses to the periphery of the tumor ranged from 800 to 2,400 cGy (median 1, 600 cGy) prescribed to the 50% to 80% isodose line (median 80%). After a median radiographic follow-up of 49 months (range 4 to 110 months), 11 tumors were smaller, 17 were stable, and one had evidence of progression (at 41 months). The 5-year local disease control rate (Kaplan-Meier estimate) was 94%. Acute complications were minimal, with only two patients experiencing nausea and vomiting after the procedure. Long-term complications included new or progressive trigeminal and facial nerve deficits with estimated 5-year incidences of 15% and 32%, respectively. Subjective hearing reduction or loss occurred in 14 (74%) of the 19 patients who had useful hearing prior to treatment. Five patients died from unrelated causes. These results suggest that linac SRS provides excellent short-term tumor control rates. Since there was a high risk of cranial nerve neuropathy, we do not recommend using only computed tomography-based planning and high prescription doses. Int. J. Cancer (Radiat. Oncol. Invest.) 90, 145-151 (2000).

Adult↗
PubMed2000

Measurement of tissue electrical impedance confirms stereotactically localized internal segment of the globus pallidus during surgery.

Lesions surgically made in the internal segment of the posteroventral globus pallidus (Gpi) reduce many medically intractable symptoms in patients with Parkinson's disease. The Gpi is localized for pallidotomy by stereotactic procedures. We sought to confirm the stereotactically localized Gpi segment by measuring impedance between the tip of an active electrode that was advanced toward the target and a remote reference electrode. A stereotactic instrument was used to place an active electrode in 53 conscious patients undergoing pallidotomy. The electrode was manually advanced slowly toward the Gpi segment by a microdrive. Impedance was measured every 10 mm initially and every 1 mm in the final 10 mm of the electrode's advancement, using an impedance monitor interconnected with a lesion generator. Measurements were continued for several millimeters after each patient's target was reached. Impedance values ranged from 250 to 350 ohms throughout of the electrode passage. Impedance increased by 25-35 ohms at 1-3 mm before the center of the target and then dropped abruptly when the electrode passed the target. Impedance values depended strongly on the electrode's configuration. The impedance measurement confirmed the location of each surgical target identified by stereotactic navigation. The accuracy of the impedance measurement is acceptable, and the procedure can be recommended as an aid to confirm the stereotactically localized Gpi during neurological surgery.

Adult↗
PubMed2000

Anti-sense oligonucleotide of p21(waf1/cip1) prevents interleukin 4-mediated elevation of p27(kip1) in low grade astrocytoma cells.

Elevation of the cyclin-dependent kinase (cdk) inhibitor, p27(kip1) is necessary for Interleukin (IL)-4-mediated growth arrest of human low grade astrocytoma (RTLGA) cells and occurs at 24 h of treatment. Pathways involved in IL4 alteration of p27(kip1) are unknown, however. Here we investigated whether other cdk inhibitors contributed to the actions of IL-4 on RTLGA cells. By 12 h of IL-4 treatment, both cdk4 and cdk2 kinase activities against the retinoblastoma protein (pRb) were reduced and nuclear entry of pRb was prohibited. Twelve-hour cdk complexes contained elevated p21(waf1/cip1) but not p27(kip1), p15(ink4B) or p16(ink4A). IL-4 increased p21(waf1/cip1) but not p27(kip1) mRNA levels, and stimulated luciferase activity of a p21(waf1/cip1) promoter-luciferase reporter. In p53-mutant WITG3 cells, IL-4 did not alter p21(waf1/cip1) mRNA and promoter-luciferase activity or p27(kipl) protein, suggesting a need for functional p53. STAT6 phosphorylation by IL-4, however, occurred in both p53-mutant WITG3 and p53-functional RTLGA cells. Pre-treatment of RTLGA with anti-sense but not missense p21(waf1/cip1) oligonucleotide prior to IL-4: (a) restored cdk activities; (b) reduced cdk4-associated p21(waf1/cip1) levels; (c) prevented p27(kipl) elevation; and (d) reversed growth arrest. These results are the first to suggest that p21(waf1/cip1) is essential for IL-4-mediated elevation of p27(kip) and growth arrest of astrocytoma cells.

Astrocytoma↗
PubMed2000

Local control and overall survival in atypical meningioma: a retrospective study.

PURPOSE: To evaluate local control and overall survival after primary surgery for patients with atypical meningiomas. METHODS AND MATERIALS: From the Department of Pathology database, we identified 491 cases of meningioma treated at the Cleveland Clinic Foundation from 1979 through 1995. Thirty-three were diagnosed with atypical meningioma. Eleven of the excluded patients had incomplete records, were lost to follow-up, or received treatment elsewhere. Of the 22 evaluable patients, 15 underwent gross total resection (GTR), 4 had a subtotal resection (STR), and 3 had a resection of unknown extent. Eight patients received radiation therapy (2 after initial resection and 6 after at least one recurrence). The median radiation dose was 5,400 cGy (range 3,500-5,940). The median age at presentation was 55.5 years, the male:female ratio was 14:8, and 19/22 patients had a Karnofsky performance score (KPS) > or =80. The independent variables analyzed for overall survival and local control were gender, KPS (> or =80 vs. < 80), extent of surgery (GTR vs. STR or unknown extent of surgery), and postoperative radiation therapy. RESULTS: Median survival was 10.6 years, with a median follow-up of 5.5 years (range 1.5-14.8). Eight of the 22 patients had local recurrence, including 2/15 with GTR, 3/4 with STR, and all 3 patients who underwent resection of unknown extent. At 10 years, patients with GTR had a higher local control rate than those who had either a STR or a resection of unknown extent (87% vs. 17%; p = 0.02). The 5- and 10-year overall survival rates for the entire group were 91% and 76%, respectively. Patients who had GTR had 5- and 10-year overall survival of 87% and 87%, respectively. Patients with STR or resection of unknown extent had 5- and 10-year overall survival rates of 100% and 75%, respectively. CONCLUSION: In patients with atypical meningiomas, gross total resection is associated with a lower recurrence rate than in subtotal resection.

Analysis of Variance↗
PubMed2000

In vivo expression of the interleukin 4 receptor alpha by astrocytes in epilepsy cerebral cortex.

We reported previously that non-neoplastic astrocytes (derived from brain tissues of patients with epilepsy) expressed interleukin 4 receptor alpha (IL-4Ralpha) and responded to interleukin 4 (IL-4) in culture. To determine whether reactivity of cultured astrocytes was relevant to primary tissue, we investigated IL-4Ralpha expression in specimens of non-neoplastic cerebral cortex removed for surgical treatment of intractable epilepsy compared to specimens of glial tumours, which have been reported to contain IL-4Ralpha. Freshly frozen tissues from eight cases (four epilepsy, four malignant astrocytoma) were evaluated for IL-4Ralpha expression by reverse-transcriptase polymerase chain reaction (RT-PCR), Southern blotting, and double-labelled immunohistochemistry with antibodies to IL-4Ralpha and glial fibrillary acidic protein (GFAP). IL-4Ralpha mRNA was detectable in both non-neoplastic and neoplastic tissues, whereas interleukin 2 receptor gamma chain (IL-2Rgammac) mRNA was not found. By immunohistochemistry, IL-4Ralpha protein co-localized to cells displaying GFAP and astrocytic morphology in epilepsy tissues. As anticipated, IL-4Ralpha was detectable in astrocytoma, but, surprisingly, was also observed in GFAP-positive, non-neoplastic "reactive" astrocytes adjacent to tumour. Results are consistent with the concept that non-neoplastic epilepsy astrocytes express IL-4Ralpha in situ, thus confirming in vitro studies and implying IL-4 sensitivity in vivo.

Actins↗
PubMed2000

Interleukin-13 sensitivity and receptor phenotypes of human glial cell lines: non-neoplastic glia and low-grade astrocytoma differ from malignant glioma.

Many of the actions and receptor components of interleukin-13 (IL-13), a pleiotrophic cytokine with immunotherapeutic potential, are shared with IL-4. Because human low-grade astrocytoma cells express IL-4 receptors and their growth is arrested by IL-4, we speculated that IL-13 sensitivity and receptor expression might also be present. The purpose of the current study was to investigate IL-13 receptor components and sensitivity in a series of glial cell lines derived from adult human non-neoplastic cerebral cortex, low-grade astrocytoma, anaplastic astrocytoma, and glioblastoma multiforme. Unlike peripheral blood lymphocytes (PBL), glial cells did not express IL-2 receptor gamma chain. IL-13 receptor alpha-1 (IL-13Ralpha1), however, was present in 11/13 glial lines and PBL. Deficient cell lines were all glioblastoma-derived. All anaplastic astrocytoma and glioblastoma but not other glial lines or PBL expressed IL-13 receptor alpha-2 (IL-13Ralpha2). In non-neoplastic glia, low-grade, and anaplastic astrocytoma, IL-13 decreased DNA synthesis, an effect reversible with antibody to IL-4Ralpha. Results indicate that low-grade astrocytoma cells resemble non-neoplastic glia in terms of IL-13 sensitivity and IL-4Ralpha/IL-13Ralpha1 receptor profile but alterations occur with malignant progression. Glioblastoma cells were uniformly insensitive to IL-13 and, unlike other glia, failed to phosphorylate STAT6 after IL-13 challenge. Data suggest that IL-13 and analysis of IL-13 receptors may have clinical application in glial tumors.

Astrocytoma↗
PubMed2000

Radiation-induced meningioma: a distinct molecular genetic pattern?

Radiation-induced meningiomas arise after low-dose irradiation treatment of certain medical conditions and are recognized as clinically separate from sporadic meningioma. These tumors are often aggressive or malignant, they are likely to be multiple, and they have a high recurrence rate following treatment compared with sporadic meningiomas. To understand the molecular mechanism by which radiation-induced meningioma (RIM) arise, we compared genetic changes in 7 RIM and 8 sporadic meningioma (SM) samples. The presence of mutations in the 17 exons of the neurofibromatosis type 2 (NF2) gene, which has been shown to be inactivated in sporadic meningiomas, was analyzed in RIM and SM using single-strand conformation polymorphism (SSCP) and DNA sequencing. In contrast to SM, which showed NF2 mutations in 50% of specimens, no mutations were found in RIM. In addition, Western blot analysis of schwannomin/merlin protein, the NF2 gene product, demonstrated protein levels comparable to normal brain in 4/4 RIM tumor samples analyzed. Loss of heterozygosity (LOH) of genomic regions, which were reported for SM, was also analyzed in all cases of RIM using 22 polymorphic DNA markers. Allele losses were found on chromosomes 1p (4/7), 9p (2/7), 19q (2/7), 22q (2/7), and 18q (1/7). From these observations we conclude that unlike sporadic meningiomas, NF2 gene inactivation and chromosome 22q deletions are far less frequent in RIM, and their role in meningioma development following low dose irradiation is less significant. Other chromosomal lesions, especially loss of 1p, possibly induced by irradiation, may be more important in the development of these tumors.

Adult↗