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J M Bruner

Publications and source records attributed to J M Bruner.

At least 73 records · Page 4Linked to original sources
PubMed1994

Basic fibroblast growth factor and fibroblast growth factor receptor I are implicated in the growth of human astrocytomas.

Malignant astrocytomas are highly invasive, vascular neoplasms that comprise the majority of nervous system tumors in humans. A strong association has previously been made between malignancy in human astrocytic tumors and increased expression of certain fibroblast growth factor (FGF) family members, including basic and acidic FGF. The influence of endogenous basic FGF on glioblastoma cell growth in vitro was evaluated using basic FGF-specific antisense oligonucleotides. These studies indicated that human glioblastoma cell growth in vitro, can be inhibited by suppressing basic FGF expression. Human astrocytomas also exhibited changes in FGF receptor (FGFR) expression during the course of their progression from a benign to a malignant phenotype. FGFR2 (bek) expression was abundant in normal white matter and in all low grade astrocytomas, but was not observed in glioblastomas. Conversely, FGFR1 (flg) expression was absent or barely detectable in normal white matter, but was significantly elevated in glioblastomas. Glioblastomas also expressed an alternatively spliced form of FGFR1 containing two immunoglobulin-like disulfide loops (FGFR1 beta), whereas normal human adult and fetal brain expressed a form of the receptor containing three immunoglobulin-like disulfide loops (FGFR1 alpha). Intermediate grades of astrocytic tumors exhibited a gradual loss of FGFR2 and a shift in expression from FGFR1 alpha to FGFR1 beta as they progressed from a benign to a malignant phenotype. The underlying cytogenetic changes that contribute to these alterations are not entirely understood, but abnormalities in the p53 tumor suppressor gene may influence expression of bFGF as well as the FGFR. These results suggest that alterations in FGFR signal transduction pathways may play a critical role in the malignant progression of astrocytic tumors.

Astrocytes↗
PubMed1994

Immunohistochemical localization of plasminogen activator inhibitor type 1 in human brain tumors.

We investigated the immunohistochemical localization of plasminogen activator inhibitor type 1 (PAI-1) in surgical specimens of 41 human intracranial tumors. Malignant tumors (7 glioblastoma multiforme, 5 anaplastic gliomas, 4 malignant meningiomas, and 9 metastatic tumors) showed consistently stronger PAI-1 immunohistoreactivity than benign or low-grade tumors (5 low-grade gliomas, 8 benign meningiomas, and 3 Schwannomas). Strong PAI-1 positivity was confined to glomeruloid-shaped proliferative vessels seen in high-grade gliomas and metastatic tumors. Blood vessels near necrotic foci and some zones of necrosis also showed strong PAI-1 positivity. PAI-1 localizes in the vascular basement membrane and perivascular connective tissue, while endothelial cells themselves show weak positivity. None of the specimens showed PAI-1 reactivity within the tumor cells per se. Localization of PAI-1 in proliferating vessels suggests that PAI-1 may be involved in angiogenesis.

Brain Neoplasms↗
PubMed1994

Prognostic significance of p53 immunoreactivity in adult patients with supratentorial fibrillary astrocytic neoplasms.

The prognostic significance of p53 immunoreactivity in adult patients with supratentorial fibrillary astrocytic neoplasms was examined by Kaplan-Meier survival analysis. Using a monoclonal antibody that reacts with both mutant and wild-type p53 protein (PAb 1801), reactivity was assessed immunohistochemically in specimens from the first diagnosis of astrocytic neoplasm in 95 patients: 26 astrocytomas (A), 19 anaplastic astrocytomas (AA), and 50 glioblastomas multiforme (GBM). Overall, 53% of cases exhibited any p53 nuclear immunoreactivity, with approximately the same proportion in each histologic grade. Survival was measured from diagnosis to death or last follow-up and ranged from 3 months to 9 years. Histologic grade was a powerful prognostic variable for this group of patients (p < 0.001), with median survivals of 88, 18, and 9 months for A, AA, and GBM patients, respectively. In contrast, patients with p53-immunoreactive or -nonimmunoreactive neoplasms had median survival times of 18 or 15 months, respectively (p = 0.21). These results indicate that p53 immunoreactivity was not prognostically significant in this group of adult patients with supratentorial fibrillary astrocytic neoplasms, although a small difference in survival cannot be excluded.

Adult↗
PubMed1994

Prognostic significance of bromodeoxyuridine labeling in primary and recurrent glioblastoma multiforme.

To evaluate the prognostic significance of bromodeoxyuridine (BUdR) labeling index (LI) and to estimate tumor proliferative potential, BUdR LI was examined in 98 patients having a primary diagnosis of glioblastoma multiforme (GBM); 55 underwent infusion of 200 mg/m2 of BUdR at the time of the primary resection and 49 underwent infusion at the time of the second resection. The tumors of six patients were labeled at both operations. The tumor specimens were stained with hematoxylin and eosin for histopathology and by immunohistochemical methods to determine the ratio of labeled to unlabeled cells, i.e., BUdR LI. The median BUdR LIs for the primary and recurrent GBM were significantly different at 6.8 and 2.6%, respectively (P < 0.0001). However, there was no significant association between BUdR LI at the first or second operation and survival (log rank, P = 0.12; Cox regression analysis, P = 0.91; log rank, P = 0.55; Cox regression analysis, P = 0.17, respectively). Patients who underwent a second operation within 10 months of the first operation had a lower BUdR LI than did patients with a longer interval between procedures (P = 0.078; Spearman rank correlation, 0.26). The aggressive biological behavior of GBM is dependent on complex cellular kinetics, not simply on the number of cells within the S phase of the cell cycle. Caution should be used when determining prognosis with BUdR LI in GBM.

Adult↗
PubMed1994

Neuropathology of malignant gliomas.

Astrocytomas are the most common primary gliomas, with the highly anaplastic glioblastoma multiforme being the most frequently occurring astrocytoma. Distinctive histological features permit astrocytomas to be graded into levels of anaplasia, and these histological grades correlate with biological behavior and patient prognosis. However, there is also a strong correlation between patient age, tumor grade, and prognosis. More objective indicators of tumor proliferative potential, such as BUdR or Ki-67 LI, are currently being investigated with the hope that these will be a more accurate means of predicting patient survival. Oligodendrogliomas are a much less common primary glioma, with a generally better survival rate than astrocytomas. However, grading systems for oligodendrogliomas are not well defined. For any type of glioma, subsequent surgery after radiation therapy may be required for treatment of therapeutic effects or for therapy planning at recurrence. The histological changes observed in these post-therapy biopsy specimens or resections may be difficult to distinguish from reactive changes that can simulate recurrent tumor and vice versa.

Adult↗
PubMed1993

Use of [18F]fluorodeoxyglucose positron emission tomography in patients with primary malignant brain tumors.

In patients with malignant gliomas, [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) may discriminate tumor progression from radionecrosis. We evaluated data from 50 patients undergoing FDG-PET for suspicion of tumor progression. Forty-nine were treated with surgery, 48 with radiotherapy, and 37 with chemotherapy. Twenty-one had intensive radiotherapy with either three daily treatments in two 5-day periods and intravenous carboplatin (17) or interstitial brachytherapy or stereotactic radiotherapy. Twenty underwent surgery after magnetic resonance imaging/FDG-PET; 9 demonstrated increased uptake of FDG and evidence of tumor, whereas 6 had decreased uptake and no evidence of tumor. In 5 patients, there was no correlation (all had intensive radiotherapy). In 17 patients who received bromodeoxyuridine intravenously just before surgery, the bromodeoxyuridine labeling index corresponded to the histological appearance in all but 2 patients (both had received intensive radiotherapy). In 30 patients without surgery, decreased uptake of FDG suggested prolonged survival; increased uptake of FDG did not predict survival. Eight of 10 with intensive radiotherapy had decreased label uptake. We conclude FDG-PET for evaluation of patients with possible recurrent tumors requires more study. In patients with intensive radiotherapy, FDG-PET results cannot be correlated accurately with tumor progression.

Adult↗
PubMed1993

Immunoglobulin heavy chain rearrangements in primary brain lymphomas. A study using PCR to amplify CDR-III.

Primary brain lymphomas (PBLs) have only rarely been analysed for immunoglobulin heavy chain (IgH) rearrangements. In this study, DNA was extracted from paraffin blocks in 23 cases of PBL and examined for IgH rearrangements using the polymerase chain reaction (PCR) to amplify the complementarity-determining region III (CDR-III) of rearranged IgH genes. Fifteen of the cases were phenotyped on paraffin-embedded tissue using a pan-B and pan-T antibody (L26 and UCHL-1, respectively). The remaining eight cases were not phenotyped for lack of tissue. For comparison, we used DNA extracted from paraffin blocks of normal brain, lymph nodes with lymphoid hyperplasia, and non-lymphoid malignancies. PCR products were examined by polyacrylamide gel electrophoresis. Among the ten B-cell PBL; four had a pattern indicative of IgH rearrangement, one had a germline pattern, and five had no detectable PCR products. Among the five T-cell PBLs, one had a germline pattern and four had no detectable products. Among the eight untyped PBLs, two had IgH rearrangement, four had a germline pattern, and two gave no detectable products. DNA from non-lymphoid tissues gave a consistent germline pattern, while DNA from polyclonal lymphoid populations (lymph node) had a pattern of polyclonal IgH rearrangement. In a dilution study, a clonal rearrangement could be detected as long as the clone's DNA constituted at least 10 per cent of the total DNA. PCR to amplify CDR-III can be successfully applied to DNA extracted from paraffin blocks, and it detected a clonal rearrangement in 50 per cent of cases that gave a detectable pattern.(ABSTRACT TRUNCATED AT 250 WORDS)

Base Sequence↗
PubMed1993

Distribution of p53 protein expression in gliosarcomas: an immunohistochemical study.

The wild-type p53 gene product is a nuclear phosphoprotein that suppresses cell and tumor growth. Mutations of the p53 gene are by now the most frequently recognized genetic alterations in human malignancies and occur in many types of carcinomas as well as in astrocytomas and sarcomas. Wild-type p53 protein has a short half-life, is present in very low quantities in normal cells and cannot be detected immunohistochemically. Mutant p53 proteins have longer half-lives and are usually present in immunohistologically detectable amounts. It is generally agreed that the presence of p53 immunostaining indicates the presence of an abnormal p53 protein and is strongly suggestive of a mutation in the p53 gene. In this study, we stained paraffin sections from eight samples of gliosarcomas from seven patients with an antibody to p53. All tumors contained p53-immunoreactive nuclei in both the glial and the sarcomatous component. In five tumors, a majority of nuclei was positive in the sarcomatous component while only a minority of nuclei was positive in the glial areas. In one tumor, the reverse was seen. In another tumor, approximately half the nuclei were positive in both components and in one tumor, only a minority of nuclei were positive in either component (this lesion was the recurrence of a tumor in which the majority of the sarcoma's nuclei had been positive). These data indicate that p53 mutations may play a role in the pathogenesis of gliosarcomas and suggest an origin of both the glial and sarcomatous components from a common progenitor.

Adult↗
PubMed1993

Detection of p53 alterations in human astrocytomas using frozen tissue sections for the polymerase chain reaction.

The polymorphism of amino acid residue 72 on the human p53 tumor-suppressor gene is a useful marker for detecting intragenic loss of heterozygosity (LOH). We examined the LOH of the p53 gene in human malignant astrocytomas by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using DNA extracted from frozen tissue sections under histologic examination. Eleven of 16 informative cases (69%) of the malignant astrocytomas were found to have LOH in the p53 gene. Sequential frozen sections were analyzed by immunohistochemistry using anti-p53 antibody PAb1801 to detect overexpression of the p53 protein, which is presumably altered if it is detectable. Ten of the 11 cases that had LOH of the p53 gene overexpressed the p53 protein. Moreover, 4 of the 11 patients with LOH of the p53 gene developed a second neoplasm in addition to an astrocytoma, possibly indicating genetic instability in these patients. These data suggest that alterations of the p53 gene may play an important role in the genesis of malignant astrocytoma. The combination of the PCR-RFLP method and immunohistochemical analysis using frozen tissue sections is a practical diagnostic tool for examination of human malignancies, including astrocytomas. astrocytomas.

Astrocytoma↗
PubMed1993

The correlation of two argyrophilic nucleolar organizer region counting methods with bromodeoxyuridine-labeling index: a study of metastatic tumors of the brain.

Bromodeoxyuridine (BrdU) is a thymidine analog that is incorporated into cellular DNA in the synthetic phase. The BrdU-labeling index (BLI) thus reflects the S-phase fraction. The argyrophilic nucleolar organizer regions (AgNORs) are silver-stained granules that have been correlated with ploidy and/or S-phase fraction. Two AgNOR counting methods have been proposed to distinguish between ploidy and S-phase fraction: the mean AgNOR (mAgNOR) count (the mean number of AgNOR granules in 100 cells), which is believed to reflect ploidy, and the AgNOR proliferative index (pAgNOR) (the percentage of cells exhibiting five or more AgNOR granules per nucleus), which is believed to reflect S-phase fraction. To evaluate the latter hypothesis we studied 19 tumors metastatic to the brain in patients who had received preoperative low-dose BrdU injections. Formalin-fixed, paraffin-embedded sections of the resected tumors were stained using the indirect immunoperoxidase technique and a monoclonal antibody to BrdU. The BLI was determined by counting 1,000 tumor cells in each case; AgNOR silver staining was performed on sections of the same blocks studied for BLI. The correlation between pAgNOR counts and BLI was statistically significant (r = .649, P = .003). No statistically significant correlation could be obtained between mAgNOR counts and BLI (r = .421, P = .17). We conclude that the pAgNOR count can reliably reflect the proliferative activity of cells. The method can prove beneficial in situations in which cell kinetic analysis is needed and in which invasive procedures, such as BrdU injection, are not feasible or are contraindicated.

Adult↗
PubMed1993

Leptomeningeal toxoplasmosis after allogeneic marrow transplantation. Case report and review of the literature.

A 37-year-old woman with chronic myelogenous leukemia underwent allogeneic bone marrow transplantation with CD8-depleted marrow from an HLA-identical sister. On day 43 post-transplant, the patient developed a headache and became lethargic and tremulous. Magnetic resonance imaging (MRI) of the brain showed abnormal meningeal and superficial parenchymal enhancement anteriorly. The spinal fluid had an elevated protein level with normal glucose and a neutrophilic pleocytosis. At autopsy, Toxoplasma meningoencephalitis was seen. On review of the literature, headache and confusion at 1-2 months post-transplant are common presenting signs of central nervous system toxoplasmosis. The predominance of neutrophils in the spinal fluid in this patient probably reflects the meningeal component of the infection and is an unusual finding. The presentation of toxoplasmosis in marrow transplant recipients is quite pleomorphic, and a definite diagnosis is difficult to obtain antemortem. Empiric therapy with pyrimethamine and sulfadiazine should be considered for marrow transplant recipients with neurologic deficits for which there is no other apparent etiology.

Adult↗
PubMed1993

Neuropathology, cell biology, and newer diagnostic methods.

Recent publications emphasized the correlation between molecular events in brain tumors and clinical outcome. Alterations in tumor-suppressor genes, growth factors, and enzyme systems have been previously described in gliomas; the relationships between these various changes and tumor grade, growth rate, and response to therapy are subjects of current investigations. Loss of genetic heterozygosity on chromosomes 10 and 17p, amplification and rearrangement of the epidermal growth factor receptor gene, express ion of its protein product, and changes in chromosomes 9, 19, and the enzyme system protein kinase C are the specific molecular events that were compared. Changes in chromosome 22 were correlated with histologic features of meningioma. Various methods of measuring tumor cell proliferation (proliferating cell nuclear antigen, bromodeoxyuridine, Ki-67, nucleolar organizer regions, and DNA flow cytometry) are being compared with each other and correlated with clinical outcome in an attempt to validate these methods and to discover the most relevant one. More recently described tumor types continue to be characterized using standard techniques and some of these newer methods. Neurocytoma has been morphologically and immunochemically defined as a neuronal neoplasm, but determination of the full compass of its clinical behavior and position in the continuum of cerebral neuronal tumors awaits additional studies.

Brain Neoplasms↗
PubMed1993

The prognostic value of human chorionic gonadotropin expression in colorectal adenocarcinomas. An immunohistochemical study of 102 stage B2 and C2 nonmucinous adenocarcinomas.

Several recent studies have detected human chorionic gonadotropin (hCG) expression in colorectal adenocarcinomas and have concluded that its expression is an adverse prognostic indicator. The patient population and length of follow-up has varied. Therefore, we reviewed a defined group of cases with long-term (> 5 years) follow-up. We studied 102 stage B2 and C2 nonmucinous adenocarcinomas immunohistochemically for the production of hCG. Expression of hCG was detected in paraffin sections, including tumor and adjacent mucosa, using immunolabeling with a polyclonal rabbit antibody and the avidin-biotin-peroxidase complex technique. Cytoplasmic positive staining was evaluated semiquantitatively in every low-power microscopic field containing tumor. Expression of hCG was noted in at least one field in 42% (43/102) of the carcinomas. There was no expression in adjacent mucosa. Although the staining was usually focal (< 5% of tumor cells), some cases did stain diffusely. There was no significant correlation of hCG expression with survival, stage, differentiation, age, race, sex, or site of tumor. We therefore conclude that hCG expression is not a significant prognostic indicator in stage B2 and C2 colorectal carcinomas.

Adenocarcinoma↗
PubMed1993

p53 protein immunostaining in routinely processed paraffin-embedded sections.

Mutation of the p53 tumor suppressor gene is the most common genetic alteration in human tumors. The altered protein product of the mutant gene is stabilized in tumor cells and can be detected using monoclonal antibody immunohistochemistry. We report a technique for immunostaining of the altered p53 protein in routinely processed paraffin-embedded tissue sections, comparing this method with a frozen-section immunostain method for concordance. Similarly processed tumor cell lines with known mutations or deletions of the p53 gene served as positive or negative controls. The results in 25 human gliomas and 20 colorectal carcinomas showed a 100% correspondence of positive reactivity in the colorectal carcinomas and an 83% correspondence in the gliomas. In no case did the paraffin-embedded sections react in the absence of frozen section reactivity (that is, there were no false positives). Three of 18 gliomas showed reactivity in frozen sections without reactivity in the companion paraffin-embedded sections. This discrepancy could have been caused by technical factors such as length of fixation time. We propose that this new paraffin-embedded section immunostaining method will be of value as a screening technique for the investigation of p53 mutations in archived human tumors. The data thus obtained may then be correlated with clinical information and perhaps be of value in diagnosis or predicting outcome for various human cancers.

Adenocarcinoma↗
PubMed1992

Alternative splicing of neurofibromatosis type 1 gene transcript in malignant brain tumors: PCR analysis of frozen-section mRNA.

The neurofibromatosis type 1 (NF1) gene encodes a 360-residue region showing significant homology to the catalytic domains of both mammalian GTPase-activating protein (GAP) and yeast IRA protein. The product of the GAP-related domain of the NF1 gene (NF1-GRD) has been shown to stimulate ras GTPase and consequently to inactivate ras protein. We previously reported that the NF1-GRD has two types of transcripts, type I and type II, which are generated by an alternative splicing mechanism, and that the differential splicing of the NF1-GRD may be related to differentiation of neuroectodermal cells. Here we examined the differential expression of type I and type II transcripts of NF1-GRD in clinical samples of supratentorial malignant brain tumors by the RNA-polymerase chain reaction (PCR) method using frozen tissue sections. Our observations revealed that normal cerebrum predominantly expressed the type II NF1-GRD transcript, whereas primitive neuroectodermal tumors predominantly expressed the type I transcript. Additionally, although the type I/type II ratio in astrocytomas varied widely among tissue samples, all glioblastomas showed higher type I/type II ratios than adjacent brain samples. The RNA-PCR analysis using frozen tissue sections is a useful and sensitive method for detecting genetic markers in clinical tissue samples.

Astrocytoma↗
PubMed1992

Intracranial ependymoma in children: analysis of prognostic factors.

Between 1955 and 1986, 25 children (aged 2 weeks to 15 years) were treated for intracranial ependymoma at M.D. Anderson Cancer Center. Nine patients had supratentorial primaries (5 high-grade, 4 low-grade), and 16 had infratentorial primaries (9 high-grade, 7 low-grade). Five patients had gross complete resection and 20 had incomplete resection. Seven patients received craniospinal irradiation (25-36 Gy to the neuro-axis, 45-55 Gy to tumor bed), 12 received local field irradiation (29-60 Gy, median 50 Gy). Five infants had adjuvant chemotherapy without radiotherapy, and 6 children had post-radiotherapy adjuvant chemotherapy, and 12 patients had salvage chemotherapy with various agents and number of courses. Eight patients are alive, disease-free and without relapse from 1 year to 12 1/2 years from diagnosis (median 42 months). The primary failure pattern was local recurrence. The data suggest that 1) the long-term cure rate of children with ependymoma is suboptimal; 2) histologic grade may be of prognostic importance for supratentorial tumors; 3) prognosis appears worse for girls and infants under 3 years of age; 4) in well-staged patients routine spinal irradiation could be omitted; 5) the role of adjuvant chemotherapy is unclear.

Adolescent↗