| 1. |
- Andersson, Ulrika, et al.
(författare)
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Epidermal growth factor receptor family (EGFR, ErbB2-4) in gliomas and meningiomas
- 2004
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Ingår i: Acta Neuropathologica. - : Springer Science and Business Media LLC. - 0001-6322 .- 1432-0533. ; 108:2, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- Overexpression of epidermal growth factor receptor (EGFR, ErbB1) correlates with enhanced malignant potential of many human tumor types including glioblastoma multiforme. The significance of EGFR expression in meningiomas is, however, unclear. Reports regarding the other EGFR family members, ErbB2-4, in brain tumors are sparse. In this study, the expression of the EGFR family members was analyzed in relation to various parameters for the clinical importance of these receptors in 44 gliomas and 26 meningiomas. In gliomas, quantitative real-time reverse transcription (RT)-PCR revealed the highest EGFR mRNA expression in high-grade gliomas, while ErbB2 and ErbB3 mRNA were detected only in a few high-grade gliomas. In contrast, ErbB4 expression was most pronounced in low-grade gliomas. Immunohistochemistry showed significantly higher EGFR protein expression in high-grade gliomas compared to low-grade gliomas (P= 0.004). ErbB2 protein expression was mainly seen in high-grade gliomas. ErbB3 protein expression was low in all gliomas analyzed. ErbB4 protein expression was significantly higher in low-grade gliomas than in high-grade gliomas (P= 0.007). In meningiomas, quantitative real-time RT-PCR revealed expression of EGFR, ErbB2, and ErbB4 mRNA in the majority of the tumors. ErbB3 was detected in only one of the meningiomas analyzed. Immunohistochemistry demonstrated high ErbB2 protein expression in meningiomas. An intriguing observation in astrocytomas and oligodendrogliomas grade II, was a significantly decreased overall survival for patients with high EGFR protein expression (P= 0.04). The high ErbB4 expression in low-grade compared to high-grade gliomas might suggest that ErbB4 acts as a suppressor of malignant transformation in brain tumors, which is in line with previous studies in other tumor types.
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| 2. |
- Andersson, Ulrika, et al.
(författare)
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Heterogeneity in the expression of markers for drug resistance in brain tumors
- 2004
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Ingår i: Clinical Neuropathology. - 0722-5091. ; 23:1, s. 21-27
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Tidskriftsartikel (refereegranskat)abstract
- Brain tumors, in general, display a multidrug-resistant phenotype. This study evaluated the immunohistochemical expression and distribution of P-glycoprotein (Pgp), multidrug resistance protein (MRP1), lung resistance protein (LRP) and O6 methylguanine-DNA methyltransferase (MGMT) in low- and high-grade astrocytoma, oligodendroglioma and in different subgroups of meningioma. The results revealed a marked heterogeneity in the expression and distribution among the analyzed tumors. In astrocytoma and oligodendroglioma, Pgp and MRP1 were observed in the capillary endothelium and in scattered tumor cells, whereas LRP occurred only in tumor cells. A pronounced expression of MGMT was found independent of the histopathological grade. An enhanced expression of MRP1 and LRP in astrocytoma and oligodendroglioma were more often evident in older patients (> 50 years). Survival analysis suggested a markedly decreased overall survival for patients suffering from low-grade glioma overexpressing Pgp. In meningioma, a heterogeneous expression of Pgp, MRP1, LRP and MGMT was seen with the most prominent staining localized to the capillary endothelium. Pgp was significantly more often overexpressed (p < 0.05) in transitional compared to meningothelial meningioma. The marked heterogeneity in the expression suggests that analysis of these factors can be of importance in the selection of individualized chemotherapy, regardless of tumor type.
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| 3. |
- Andersson, Ulrika, et al.
(författare)
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Rapid induction of long-lasting drug efflux activity in brain vascular endothelial cells but not malignant glioma following irradiation
- 2002
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Ingår i: Medical Oncology. - 1357-0560 .- 1559-131X. ; 19:1, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- The influence of radiotherapy on malignant glioma multidrug resistance to chemotherapy was evaluated because patients with glioma often are treated with a combination of radiotherapy and chemotherapy. Multidrug resistance gene (MDR1, mdr1a, and mdr1b) transcripts were found in human and rat glioma cell lines. P-Glycoprotein (Pgp) was immunohistochemically detected in glioma cell lines and in the rat brain vascular endothelial cell line (RBE4). A multidrug resistance pump efflux activity assay demonstrated increased calcein efflux of RBE4 endothelial cells, but not glioma cells, 2 h after irradiation and still increased 14 d after irradiation. The increased efflux was equally inhibited by verapamil with or without irradiation. In the rat intracranial glioma model (BT4C), Pgp was demonstrated in capillary endothelial cells of the tumor tissue and surrounding normal brain, but not in tumor cells. The expression of gene transcripts or Pgp was not affected by irradiation. The results indicate that long-lasting verapamil-resistant drug efflux mechanisms are activated in brain endothelial cells after irradiation. The results might explain the poor efficacy of chemotherapy following radiotherapy and contribute to consideration of new treatment strategies in the management of malignant glioma.
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| 4. |
- Hariz, Gun-Marie, et al.
(författare)
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Does the ADL part of the unified Parkinson's disease rating scale measure ADL? An evaluation in patients after pallidotomy and thalamic deep brain stimulation.
- 2003
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 18:4, s. 373-381
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the impact of pallidotomy and thalamic deep brain stimulation (DBS) on disability of patients with advanced Parkinson's disease and investigated whether the activities of daily living (ADL) section of the Unified Parkinson's Disease Rating Scale (UPDRS) measures disability in everyday life. Nineteen patients who had pallidotomy and 14 patients who had thalamic DBS were followed for a mean of 11 months. Evaluation tools included the UPDRS as well as a generic ADL scale, called ADL taxonomy. The 13 items belonging to the ADL part of the UPDRS were classified into two categories according to whether the items described a disability or impairment. The total scores of the UPDRS Part II (ADL) were ameliorated in both the pallidotomy and the thalamic DBS groups. When analysing separately the scores from the two categories of the ADL part of the UPDRS, i.e., disability and impairment, only patients who underwent pallidotomy showed improvement in disability-related items. These findings were confirmed when evaluating the patients with the ADL taxonomy. The ADL part of the UPDRS contains a mixture of impairment- and disability-related items. This mixture may confound results when evaluating the impact of surgery on ADL.
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| 5. |
- Hariz, Gun-Marie, et al.
(författare)
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Gender differences in disability and health-related quality of life in patients with Parkinson's disease treated with stereotactic surgery
- 2003
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Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 108:1, s. 28-37
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To investigate eventual differences between women and men with Parkinson's disease (PD) before and after surgery, with respect to clinical status, disability and health-related quality of life (HRQoL). MATERIAL AND METHODS: Twenty-four men and 14 women with PD received a total of 46 surgical procedures (pallidotomy, thalamotomy and deep brain stimulation of the thalamus, pallidum or subthalamic nucleus). The impact of PD on disability and other aspects of HRQoL was analysed separately in men and women before and at a mean of 11 months after surgery, using the following assessment tools: The Unified Parkinson's Disease Rating Scale (UPDRS), the ADL Taxonomy, the Nottingham Health Profile, the Life Satisfaction Questionnaire and a Visual Analogue Scale. RESULTS: At surgery, women had a significantly longer duration of disease than men (mean: 15 vs. 10 years, P < 0.01). They had a higher stage on the Hoehn and Yahr scale and worse scores on UPDRS parts II (ADL) and IV (complications), as well as on the Schwab and England scale and on the ADL Taxonomy. Following surgery, both men and women showed improvement, but women experienced greater benefit than men in ADL, in emotions, and in social life. CONCLUSIONS: Perhaps women with PD should be offered surgery more often and earlier in the course of their disease.
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| 6. |
- Hariz, Gun-Marie, et al.
(författare)
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Impact of thalamic deep brain stimulation on disability and health-related quality of life in patients with essential tremor
- 2002
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Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 72:1, s. 47-52
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: To evaluate the impact of thalamic deep brain stimulation (DBS) on disability and health-related quality of life in patients with essential tremor.METHODS: Twenty seven consecutive patients were evaluated prospectively, before surgery and at a mean of 12 months (range 6-26) after thalamic DBS. Assessment tools included the Fahn-Tolosa-Marìn tremor rating scale (TRS), activities of daily living (ADL) taxonomy, Nottingham health profile (NHP) and the visual analogue scale (VAS) for measuring impact of disease on life. Additional information on the side effects of, and expectations from surgery was obtained by interview.RESULTS: Thalamic DBS improved the ability of the patients in eating, drinking, writing, home maintenance, hobbies, and participation in society. Activities of daily life requiring bimanual skills were less improved. The emotional condition of the patients was positively affected and the negative impact of the disease on life as a whole, and on social life was decreased. Seventy per cent of the patients considered that the surgical treatment met their expectations.CONCLUSIONS: After thalamic DBS, health-related quality of life including disability in ADL and social life were improved in patients with essential tremor.
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| 7. |
- Lenfeldt, Niklas, et al.
(författare)
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Cerebrospinal fluid pulse pressure method: a possible substitute for the examination of B waves
- 2004
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Ingår i: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 101:6, s. 944-950
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Tidskriftsartikel (refereegranskat)abstract
- Object. The appearance of numerous B waves during intracranial pressure (ICP) registration in patients with idiopathic adult hydrocephalus syndrome (IAHS) is considered to predict good outcome after shunt surgery. The aim of this study was to describe which physical parameters of the cerebrospinal fluid (CSF) system B-waves reflect and to find a method that could replace long-term B-wave analysis.Methods. Ten patients with IAHS were subjected to long-term registration of ICP and a lumbar constant-pressure infusion test. The B-wave presence, CSF outflow resistance (Rout), and relative pulse pressure coefficient (RPPC) were assessed using computerized analysis. The RPPC was introduced as a parameter reflecting the joint effect of elastance and pulsatory volume changes on ICP and was determined by relating ICP pulse amplitudes to mean ICP.Conclusions. The B-wave presence on ICP registration correlates strongly with RPPC (r = 0.91, p < 0.001, 10 patients) but not with CSF Rout. This correlation indicates that B waves—like RPPC—primarily reflect the ability of the CSF system to reallocate and store liquid rather than absorb it. The RPPC-assessing lumbar short-term CSF pulse pressure method could replace the intracranial long-term B-wave analysis.
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| 9. |
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