| 1. |
- Mosrati, Mohamed Ali, et al.
(författare)
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TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma
- 2015
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Ingår i: Oncotarget. - : IMPACT JOURNALS LLC. - 1949-2553. ; 6:18, s. 16663-16673
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Tidskriftsartikel (refereegranskat)abstract
- Telomerase reverse transcriptase (TERT) activity is up-regulated in several types of tumors including glioblastoma (GBM). In the present study, 128 primary glioblastoma patients were examined for single nucleotide polymorphisms of TERT in blood and in 92 cases for TERT promoter mutations in tumors. TERT promoter mutations were observed in 86% of the tumors and of these, C228T (-124 bp upstream start codon) was detected in 75% and C250T (-146 bp) in 25% of cases. TERT promoter mutations were associated with shorter overall survival (11 vs. 20 months p = 0.002 and 12 vs. 20, p = 0.04 for C228T and C250T, respectively). The minor alleles of rs2736100 and rs10069690 SNPs, located in intron 2 and the promotor regions, respectively, were associated with an increased risk of developing GBM (p = 0.004 and 0.001). GBM patients having both TERT promoter mutations and being homozygous carriers of the rs2853669 C-allele displayed significantly shorter overall survival than those with the wild type allele. The rs2853669 SNP is located in a putative Ets2 binding site in the promoter (-246 bp upstream start codon) close to the C228T and C250T mutation hot spots. Interleukin-6 (IL-6) expression regulated by TERT promoter status and polymorphism, what leads us to think that TERT and IL-6 plays a significant role in GBM, where specific SNPs increase the risk of developing GBM while the rs2853669 SNP and specific mutations in the TERT promoter of the tumor lead to shorter survival.
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| 2. |
- Bruhn, H., et al.
(författare)
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Improved survival of Swedish glioblastoma patients treated according to Stupp
- 2018
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Ingår i: Acta Neurologica Scandinavica. - : WILEY. - 0001-6314 .- 1600-0404. ; 138:4, s. 332-337
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Tidskriftsartikel (refereegranskat)abstract
- ObjectivesThe median survival in glioblastoma (GBM) patients used to be less than 1year. Surgical removal of the tumor with subsequent concomitant radiation/temozolomide (the Stupp regimen) has been shown to prolong survival. The Stupp protocol was implemented in the county of Jonkoping in 2006. The purpose of this study was to examine if the Stupp treatment has prolonged overall survival, in an unselected patient cohort with histologically verified GBM. Material and MethodThis study includes all patients from the county of Jonkoping, with a diagnosis of GBM from January 2001 to December 2012. Patients were divided into 2 cohorts, 2001-2005 and 2006-2012, that is before and after implementation of the Stupp regimen. By reviewing the medical case notes, the dates of the histological diagnosis and of death were identified. The median and mean overall survival and Kaplan-Meier survival analysis were calculated and compared between the 2 cohorts. ResultsThe mean survival was 110days longer in the cohort treated according to the Stupp regimen. Four patients in the 2006-2012 cohort and 1 patient in the 2001-2005 cohort are still alive. When comparing survival in patients with radical surgery vs biopsy, those that underwent radical surgery survived longer. The significance was slightly greater in the 2001-2005 cohort (mean 163 vs 344days, Pamp;lt;.001) than in the 2006-2012 cohort (mean 220 vs 397days, P=.02). ConclusionSurvival significantly improved after the implementation of the Stupp regimen in the study region of Sweden.
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| 3. |
- Haj-Hosseini, Neda, 1980-, et al.
(författare)
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5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy
- 2018
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Ingår i: Biomedical Optics Express. - : Optical Society of America. - 2156-7085. ; 9:5, s. 2284-2296
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Tidskriftsartikel (refereegranskat)abstract
- A fiber optic probe was developed for guidance during stereotactic brain biopsy procedures to target tumor tissue and reduce the risk of hemorrhage. The probe was connected to a setup for the measurement of 5-aminolevulinic acid (5-ALA) induced fluorescence and microvascular blood flow. Along three stereotactic trajectories, fluorescence (n = 109) and laser Doppler flowmetry (LDF) (n = 144) measurements were done in millimeter increments. The recorded signals were compared to histopathology and radiology images. The median ratio of protoporphyrin IX (PpIX) fluorescence and autofluorescence (AF) in the tumor was considerably higher than the marginal zone (17.3 vs 0.9). The blood flow showed two high spots (3%) in total. The proposed setup allows simultaneous and real-time detection of tumor tissue and microvascular blood flow for tracking the vessels.
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| 4. |
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| 5. |
- Haj-Hosseini, Neda, et al.
(författare)
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Detection of brain tumor using fluorescence and optical coherence tomography
- 2015
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Konferensbidrag (refereegranskat)abstract
- Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. We have previously implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid induced protoporphyrin IX (PpIX) in the gliomas. To add another dimension to the brain tumor detection and volumetric analysis of the tissue that exhibits fluorescence, optical coherence tomography was investigated on tumor specimens.Material and Methods:A fluorescence microscopy and a spectroscopy system as reported previously were used for detecting the fluorescence signals [1, 2]. A total of 50 patients have been included for intraoperative assessment of the tumor borders using the fluorescence techniques. A spectral domain OCT imaging system (TELESTO II, Thorlabs, Inc., NJ, USA) with central wavelength of 1325 nm was used to study the tissue microstructure post operatively. The system has a resolution of 13 and 5.5 μm in the lateral and axial directions, respectively. Tissue specimens from three patients undergoing brain tumor surgery were studied using the OCT system.Results and Conclusion:Using fluorescence spectroscopy the tumor could be detected with a sensitivity of 0.84 which was significantly higher than that of the surgical microscope (0.30). Brain tissue appeared rather homogeneous in the OCT images however the highly malignant tissue showed a clear structural difference from the non-malignant or low malignant brain tumor tissue which could be related to the fluorescence signal intensities.
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| 6. |
- Haj-Hosseini, Neda, et al.
(författare)
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Fluorescence Guidance for Brain Tumor Biopsies
- 2018
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Konferensbidrag (refereegranskat)abstract
- To provide guidance during stereotactic biopsy in brain tumors, fluorescence spectroscopy was used in ten patients. It was shown that the fiber optical probe could provide real-time guidance with clear fluorescence in all patients.
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| 7. |
- Haj-Hosseini, Neda, et al.
(författare)
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Fluorescence spectroscopy and optical coherence tomography for brain tumor detection
- 2016
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Konferensbidrag (refereegranskat)abstract
- Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. Recently, neurosurgical microscopes have been modified to incorporate fluorescence modules for detection of tumor when 5-aminolevulinic acid (5-ALA) is used as a contrast. We have in combination with the fluorescence microscopes implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) in the gliomas in 50 patients intraoperatively. The results show a significantly high sensitivity for differentiating tumor from the healthy tissue and distinguished fluorescence intensity levels in the tumor cell infiltration zone around the tumor. However, knowledge on association of the quantified fluorescence signals specifically in the intermediate inflammatory zone with the infiltrative tumor cells can be complemented with volumetric tissue imaging and a higher precision histopathological analysis. In this work, a spectral domain optical coherence tomography (OCT) system with central wavelength of 1325nm has been used to image the tissue volume that the fluorescence is collected from and is evaluated against histopathological analysis for a higher precision slicing. The results show that although healthy brain has a homogenous microstructure in the OCT images, the brain tumor shows a distinguished texture in the images correlated with the PpIX fluorescence intensity and histopathology.
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| 8. |
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| 9. |
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| 10. |
- Haj-Hosseini, Neda, et al.
(författare)
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Optical guidance for stereotactic brain tumor biopsy procedures-preliminary clinical evaluation
- 2017
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Konferensbidrag (refereegranskat)abstract
- During stereotactic biopsy on suspected tumors in the brain, tissue samples are harvested to determine the malignancy. To provide guidance for finding the diagnostic tumor sites and to avoid vessel rupture, an application specific probe was developed. The setup incorporated spectroscopy for detection of 5-aminolevulinic acid induced protoporphyrin (PpIX) fluorescence and blood flow using laser Doppler flowmetry. The PpIX fluorescence was significantly different in the tumor compared to the gliotic marginal zone (p < 0.05). In conclusion, the systems made real-time tumor detection and vessel tracking possible. Moreover, the autofluorescence and blood perfusion could be studied in the tumor.
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