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D A Bosch

Publications and source records attributed to D A Bosch.

At least 55 records · Page 3Linked to original sources
PubMed1997

5-year survival and clinical prognostic factors in progressive supratentorial diffuse "low-grade" astrocytoma: a retrospective analysis of 46 cases.

In order to study survival and identify prognostic factors in progressive supratentorial low grade astrocytoma, 46 cases of diffusely growing glioma (1982-1989), in which stereotactic biopsy revealed a diagnosis of astrocytoma grade II according to Kernohan, were evaluated. Only patients with definite tumour growth on consecutive CT scans were included. All patients received a full course of fractionated radiotherapy. All tumour biopsy specimens were re-evaluated according to both the Kernohan and Daumas-Duport grading systems. Follow-up for at least 5 years showed a median survival of 47.5 months (1 year 71%, 5 year 41%). In Cox' multivariate analysis 4 factors turned out to give the best fitting prognostic model for survival: age, duration of symptoms, pre-operative neurological examination and CT-contrast enhancement. Numerical scoring was performed by giving either 1 or 0 for: age > or < 40 years, symptom duration < or > 1 year, presence or absence of focal deficit, and presence or absence of CT-contrast enhancement. Combining these factors in a score ranging from 0-4 resulted in 3 distinct groups with respect to median survival (< 2:66.5 months, 2:40 months, > 2:10 months, P = 0.0015). Although 17 cases with Kernohan grade II were upgraded using Daumas-Duport criteria (13 grade III, 4 grade IV), these cases did not form a separate survival-group. Additional parameters are needed to assess prognosis by neuropathological means, as some "low-grade" tumours are less benign than others, giving rise to a variable natural history.

Adolescent↗
PubMed1997

Differential expression of CD44 splice variants in the normal human central nervous system.

Cluster of differentiation 44 (CD44) is a broadly distributed group of glycoproteins that are involved in many functions related to cell-cell and cell-matrix interactions. In the present study, the expression of the standard form of CD44 (CD44s) and of CD44 variants (CD44v) was explored immunohistochemically on frozen sections of various areas of the human CNS. The results demonstrate that CD44s epitopes are expressed predominantly by white matter astrocytes, whereas different CD44 variant molecules are present in neurons, on axonal membranes, on endothelium or on choroid plexus epithelium. Interestingly, neurons and axons differentially expressed CD44 variant epitopes but consistently lack immunoreactivity for CD44s epitopes. Another interesting finding was that some CD44 variant epitopes expressed by neurons were localized in the cytoplasm instead of on the cell membrane. The broad distribution of variant CD44 molecules in the human CNS suggests that CD44 may play an important role in many biological processes in the CNS.

Aged↗
PubMed1997

Hypofractionated radiation induces a decrease in cell proliferation but no histological damage to organotypic multicellular spheroids of human glioblastomas.

The aim of this study was to examine the effect of radiation on glioblastoma, using an organotypic multicellular spheroid (OMS) model. Most glioblastoma cell lines are, in contrast to glioblastomas in vivo, relatively radiosensitive. This limits the value of using cell lines for studying the radiation effect of glioblastomas. The advantage of OMS is maintenance of the characteristics of the original tumour, which is lost in conventional cell cultures. OMS prepared from four glioblastomas were treated with hypofractionated radiation with a radiobiologically equivalent dose to standard radiation treatment for glioblastoma patients. After treatment, the histology as well as the cell proliferation of the OMS was examined. After radiation, a significant decrease in cell proliferation was found, although no histological damage to the OMS was observed. The modest effects of radiation on the OMS are in agreement with the limited therapeutic value of radiotherapy for glioblastoma patients. Therefore, OMS seems to be a good alternative for cell lines to study the radiobiological effect on glioblastomas.

Cell Division↗
PubMed1997

Trigeminal neuralgia: comparison of two MR imaging techniques in the demonstration of neurovascular contact.

PURPOSE: To compare two magnetic resonance (MR) imaging techniques for demonstration of vascular contact with the trigeminal nerve. MATERIALS AND METHODS: Thirteen patients with unilateral trigeminal neuralgia and 50 control subjects underwent three-dimensional fast inflow with steady-state precession (FISP) and contrast material-enhanced magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) MR imaging. The images were independently reviewed by two neuroradiologists, who were blinded to the clinical details. Six of the 13 patients underwent surgery. RESULTS: Vascular contact with the trigeminal nerve at the root entry zone was seen on FISP images in 10 of 13 (77%) symptomatic nerves and in eight of 113 (7%) asymptomatic nerves (P < .001). MP-RAGE and FISP images demonstrated arterial contacts equally well. MP-RAGE images demonstrated one additional venous contact at the root entry zone in a patient with ipsilateral trigeminal neuralgia. Interobserver agreement was good for both FISP (kappa = 0.69) and MP-RAGE (kappa = 0.78) images. The presence of vascular contact at the root entry zone, seen on preoperative MR images, was confirmed in all six patients who underwent surgery. CONCLUSION: Both FISP and MP-RAGE MR imaging are useful in demonstrating vascular contact with the trigeminal nerve at the root entry zone in patients with trigeminal neuralgia.

Case-Control Studies↗
PubMed1996

Daunorubicin and doxorubicin but not BCNU have deleterious effects on organotypic multicellular spheroids of gliomas.

In the present study organotypic multicellular spheroids (OMS) were used to study the effects of chemotherapeutic agents on malignant gliomas. Compared with the frequently used cell line models, OMS have several advantages with respect to the preservation of the cellular heterogeneity and the structure of the original tumour. OMS prepared from seven glioma specimens were treated with 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), daunorubicin or doxorubicin. After exposure to these drugs, the histology and cell proliferation of the OMS were analysed by immunohistochemistry and image analysis. Furthermore, the expression of P-glycoprotein (P-gp) and multidrug resistance-related protein (MRP), which both can contribute to resistance to daunorubicin and doxorubicin, were immunohistochemically investigated. We found that OMS from gliomas are sensitive for daunorubicin and doxorubicin but not for BCNU in terms of tissue destruction and decrease in cell proliferation. In addition, all gliomas were P-gp and MRP negative, which is in accordance with the sensitivity for daunorubicin and doxorubicin. Considering the potential use of several new alternative drug delivery methods, such as intratumoural implantation of drug-impregnated polymers or liposomal encapsulation of cytostatic drugs, daunorubicin and doxorubicin might be effective in the treatment of malignant gliomas.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

[Continuous electric thalamus stimulation for the treatment of tremor resistant to pharmacotherapy].

OBJECTIVE: To determine the efficacy of continuous electrical thalamic stimulation in the treatment of pharmacotherapy-resistant tremor in patients with Parkinson's disease and essential tremor. DESIGN: Descriptive study. SETTING: Academic Medical Centre, Academic Hospital of the University of Amsterdam. METHOD: Five patients with Parkinson's disease and one with familial essential tremor suffering from pharmacotherapy-resistant tremor were treated by implantation of a four-polar stimulation electrode in the contralateral ventrolateral thalamic nucleus connected subcutaneously to a stimulator. Continuous electrical stimulation was applied in the daytime and switched off during the night. Three of the Parkinson patients were subjected to contralateral thalamotomy as well. RESULTS: Three patients (including the one with essential tremor) had complete tremor suppression during stimulation, and the other three had intermittent minimal tremor. There were no early complications (follow-up: 1 month-1 year). One patient had mild hemi-inattention and pyramidal signs due to the thalamotomy. CONCLUSION: Continuous thalamic stimulation appears to be a good alternative to thalamotomy. It renders possible bilateral surgical treatment for severe bilateral tremor.

Aged↗
PubMed1995

Expression of CD44 splice variants in human primary brain tumors.

Expression of CD44, particularly of certain splice variants, has been linked to tumor progression and metastatic potential in a number of different animal and human cancers. Although differential expression of CD44 standard epitopes (CD44s) in human brain tumors has been reported, the expression of CD44 variant exon encoded sequences (CD44v) in primary brain tumors in situ has not been studied in detail. In the present study, the expression of CD44s and CD44v epitopes was analyzed immunohistochemically on frozen sections of primary brain tumors. In addition, the expression of CD44 on cultured glioma cells was investigated by immunofluorescence flow cytometry. The results demonstrate the presence of CD44s epitopes and of CD44 splice variants containing CD44v4, v5 and v10 sequences in various types of brain tumors. A subgroup of highly malignant gliomas showed a strong (focal) expression of CD44v5. CD44v6 was absent in all brain tumors examined. CD44s appeared to be the dominant form of CD44 expressed in primary brain tumors, its expression was not correlated with tumor grade. We envisage that CD44 isoforms, in particular CD44s, may contribute to the invasive character of primary tumors by interacting with hyaluronate, one of the most abundant molecules in the extracellular matrix of the brain.

Alternative Splicing↗
PubMed1995

Human malignant astrocytes express macrophage phenotype.

Six well-characterized specimens of cultured astrocytoma cells were investigated with a panel of macrophage markers. Our results show that the macrophage markers OKM-1(CD11b), OKM5(CD36), EBM11(CD68), HAM56, Factor 13, alpha-1-antichymotrypsin, alpha-1-antitrypsin, ferritin and lysozyme are clearly reactive to neoplastic astrocytes whereas astrocytes in normal brain specimens are not reactive. In order to obtain further confirmation concerning the reactivity of tumor cells in vivo, we simultaneously measured by flow cytometric analysis DNA content and HAM56 immunoreactivity in a freshly obtained tumor specimen. In this experiment we found a marked reactivity of aneuploid cells to HAM56. The macrophage phenotype of malignant astrocytes may reflect a similarity in functions of these cells and tumor-associated macrophages which promote tumor growth via the production of growth factors and angiogenic factors. Furthermore, our findings implicate that demonstration of macrophages within malignant astrocytomas by using macrophage-specific antibodies must be cautiously considered.

Astrocytes↗
PubMed1995

Giant intracranial mucocele.

A 21-year-old man was admitted to hospital because of recent anosmia and liquorrhoea. He also complained of moderate headache and concentration problems in the past few years. On CT scan and MRI scans a big subfrontal process was seen, partially solid and partially cystic. Neurosurgical and histological findings proved that the lesion was an osteoma of the anterior skull base, concomitant with an intradurally extending mucocele.

Adult↗
PubMed1995

Long-term culture of organotypic multicellular glioma spheroids: a good culture model for studying gliomas.

Gliomas, as well as other solid tumours, contain tumour stroma composed of connective tissue, macrophages, capillaries and other non-cellular constituents. Therefore, a homogeneous culture of tumour cells alone, as is often used as a culture model for gliomas, is not ideal to study all aspects of gliomas. In the present study we describe an alternative culture model, i.e. organotypic multicellular spheroids (OMS), that histologically closely resembles the tumour in vivo. Glioma explants, obtained at surgery from five patients, were cultured on agarose to form OMS, which were cultured for up to 16 weeks. At regular intervals, OMS were fixed and histological and immunocytochemical analyses were carried out. The histology as well as the immunocytochemical characteristics of the OMS proved to be almost unchanged after a culture period of 16 weeks. In contrast to monolayer cultures, glial fibrillary acidic protein (GFAP) expression in the OMS is preserved after 16 weeks of culture. However, in OMS from three out of five patients, small GFAP-negative cells appeared in the outer cell layers between 1 and 2 weeks of culture. Furthermore, after about 6 weeks of culture, the capillaries disappeared from the OMS. After prolonged culture, tumour cell heterogeneity, the cellular composition, and the histology of the OMS still closely resembled the tumour in vivo. It is suggested that OMS provide a good long-term culture model for the study of gliomas.

Adult↗
PubMed1995

Cytolytic effects of autologous lymphokine-activated killer cells on organotypic multicellular spheroids of gliomas in vitro.

Knowledge about lymphokine-activated killer (LAK) cell infiltration and LAK cell cytotoxicity is essential to improve the effectiveness of LAK cell therapy against gliomas. In the present study, organotypic multicellular spheroids (OMS) of glioma tissue were used as a culture model to study the effects of LAK cells on gliomas. Compared to tumour cell lines and spheroids derived from tumour cell lines, OMS have several advantages with respect to preservation of tumour cell heterogeneity and the maintenance of the tumour architecture, e.g. capillaries and extracellular matrix. Four glioma specimens, obtained at surgery, were cultured directly on agarose to form OMS, which were then co-cultured with either autologous LAK cells or autologous non-activated peripheral blood lymphocytes (PBLs). After various time periods of co-cultivation, the OMS were fixed and examined both histologically and immunocytochemically. The present results showed that LAK cells infiltrated the OMS completely within 24 h of co-cultivation and severe cellular damage was observed, whereas PBLs infiltrated the OMS poorly and there was only marginal cellular damage. The present study indicates that OMS of gliomas provide an experimental model to investigate the infiltration and cytotoxicity of LAK cells on glioma tissue in vitro.

Adult↗
PubMed1994

Amplification of the anonymous marker D17S67 in malignant astrocytomas.

Loss of heterozygosity (LOH) for chromosome arms 9p, 10p, 10q, and 17p and amplification of the epidermal growth factor receptor (EGFR) gene have been identified as frequent genetic changes in malignant astrocytomas. We have found amplification of the anonymous marker D17S67 on chromosome arm 17p in 10% (3 of 30 cases) of astrocytomas of the highest malignancy grade. The tumors with D17S67 amplification displayed other genetic changes on chromosome 17, including additional amplifications and deletions. All three patients with D17S67 amplification developed severe brain edema and died within 1 month after operation.

Aged↗
PubMed1994

Analysis of mutations in the SCH gene in schwannomas.

Schwannomas are benign tumors of cranial, spinal, and other nerve sheaths that develop sporadically or are inherited as part of neurofibromatosis type 2 (NF2). The NF2 gene (SCH) on chromosome 22 has recently been identified and shown to be inactivated by mutation and allele loss in some schwannomas. However, only limited regions in the SCH coding region were examined for mutations. We have extended these studies by screening virtually all coding sequences of the SCH gene (95% coverage) and adjacent splice site sequences for the presence of mutations in 48 schwannomas. All tumors (34 vestibular schwannomas and 14 schwannomas of other locations) were additionally characterized for allele loss on chromosome 22. By PCR-DGGE screening of the 16 known exons of the SCH gene, 22 mutations were found. Most of these give rise to a premature stop codon and are expected to result in the synthesis of a truncated gene product (schwannomin). Although there was no apparent hotspot for mutations, 16 of the 22 mutations occurred in the first eight exons or adjacent splice site sequences of the SCH gene. In several vestibular as well as other schwannomas loss of one SCH allele and mutational inactivation of the second allele were identified in the same tumor. Our data indicate that the SCH gene is implicated in the development of schwannomas of all locations in the nervous system.

Alleles↗
PubMed1994

Accelerated radiotherapy in glioblastoma multiforme: a dose searching prospective study.

The EORTC Radiotherapy Cooperative Group performed a prospective phase II study in glioblastoma multiforme using accelerated radiotherapy in escalating doses. The aims of the study were to investigate acute and late toxicity as well as tumor response and survival. Only the CT-enhanced tumor zone plus a margin of 2-3 cm were treated (mean volume, 1034 +/- 477 cm3). Radiotherapy was administered with 5-18 MV photons. The radiation schedule consisted of 3 fractions of 2 Gy/day, separated with at least 4 h. The first group of patients was scheduled to receive a total dose of 42 Gy, 21 fractions in 9 days. The total dose was then escalated up to 48 Gy (24 fractions in 10 days), 54 Gy (27 fractions in 11 days) and 60 Gy (30 fractions in 12 days). The numbers of patients entered in each dose-level group were 15, 17, 18 and 16, respectively. Acute toxicity was mild, nausea/vomiting was absent in 91% of the patients. In 80% of the patients the neurological condition improved or remained stable compared with the start of radiotherapy but in 58% of the patients steroids were necessary, either increased in dose or initiated. Acute toxicity did not increase with increasing radiation doses although patients treated with 60 Gy more often required steroids than the other groups. Late toxicity was strongly suspected in 2 patients receiving 52 Gy and 56 Gy, respectively. Within the whole group of 66 patients only one recurrence outside the primary site was found.(ABSTRACT TRUNCATED AT 250 WORDS)

Brain Neoplasms↗
PubMed1994

Allele loss on chromosomes 10 and 17p and epidermal growth factor receptor gene amplification in human malignant astrocytoma related to prognosis.

Patients with high-grade astrocytomas have a poor prognosis. However, considerable variation exists within this group of patients with respect to post-operative survival. In order to determine whether genetic alterations might be of help in subdividing this group, we used allele loss on chromosomes 10 and 17p and epidermal growth factor receptor (EGFR) gene amplification in the tumours as genetic parameters and determined their prognostic value. A series of 47 malignant (grade III and grade IV) tumours were genetically characterised, and four types of tumours were found. Type 1 tumours had loss of heterozygosity on chromosome arm 17p (LOH 17p) as the sole genetic alteration. Patients with this type of tumour were relatively young (mean age 39 years) and had a median survival period of 17 months. Type 2 tumours displayed only allele loss on chromosome 10 (LOH 10), type 3 tumours had LOH 10 + LOH 17p and type 4 tumours contained LOH 10 + EGFR gene amplification. Patients with types 2, 3 and 4 tumours were older (mean ages 59, 65 and 54 years respectively) and had a shorter survival (median duration 6, 3 and 2 months respectively) than type 1 patients. Multivariate analysis indicated that the genetic subdivision was a significant prognostic variable. In this study, age proved to be of minor importance with regard to survival. Our study revealed a predominance of frontally located tumours in patients with type 1 tumours, i.e. with LOH 17p only.

Adult↗
PubMed1994

Genetic versus histological grading in stereotactic biopsies.

With diagnostic stereotactic biopsies in astrocytoma sometimes false results will be encountered. A false positive result is defined as a histological diagnosis which is afterwards proved to be untrue. Although this happens very seldom (1-2%) in characterizing the tumor type (e.g. astrocytoma versus lymphoma), there is a probability of undergrading in malignant astrocytomas due to regional heterogeneity in malignancy grade. The issue of 'sampling error' has been addressed by many authors. It was shown that undergrading in astrocytomas is a likely event in fibrillar astrocytomas that often show geographically distinct areas of well and poorly differentiated elements. In a recent study on histological grading versus genetic characterization of heterogeneous astrocytomas we published that low-grade areas within high-grade malignant astrocytomas have already the genetic features of high-grade malignancy. Therefore, particularly in stereotactic biopsies which contain relatively small samples of tumor tissue, this fact is of paramount importance. Undergrading may lead to withholding radiotherapy from the patient and to falsification of long-term survival results in series of so-called low-grade astrocytomas. We like to stress the importance of taking biopsies from different parts of the tumor, especially from parts with different density enhancement to contrast with CT scanning, and will discuss the technical advancements made in the genetic grading of astrocytomas. Particularly loss of heterozygosity of chromosome 10 and eventually amplification of the EGFR indicate a high grade of malignancy.

Adult↗