| 21. |
- Edsjö, Anders
(författare)
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Neuroblastoma Cell Differentiation: The Role of Neurotrophin Receptor Signaling and N-myc Expression
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Neuroblastoma is a tumor of sympathetic nervous system derivation, mostly afflicting young children. This thesis is focused on a group of receptor proteins for neurotrophic factors, the Trk family, and on N-Myc, a transcription factor, all important in the formation of the sympathetic nervous system as well as in determining neuroblastoma patient outcome. Expression of trkA and trkC is linked to favorable prognosis, while amplification of the N-myc gene is strongly correlated to poor outcome. The role of trkA and trkC in neuroblastoma cell differentiation was studied using neuroblastoma cell lines constitutively expressing trkA or trkC. Stimulation of the trkA- and trkC-transfected cells with their cognate ligands resulted in differentiation of both cell clones, the differentiated trkC-transfected cells lacking important neuronal features present in the differentiated trkA-transfected cells. Signaling elicited by the two receptors was studied and differences described. The possible connection between expression of N-myc and trkB, another trk family member, was tested by examination of expression of these genes in a set of neuroblastomas and neuroblastoma cell lines. Results suggested high expression of N-myc per se to be insufficient to induce trkB expression. In other experiments, retinoic acid, an agent known to induce trkB expression was added to neuroblastoma cells in combination with the ligand of TrkB, brain-derived neurotrophic factor. Data from characterization of the resulting phenotype indicated that a sympathetic neuronal differentiation did not take place in these cells and alternative explanations were suggested. N-myc expression in the developing human sympathetic nervous system was studied using in situ hybridization and the role of N-myc in neuroblastoma cell was examined, utilizing non-N-myc-amplified neuroblastoma cells with constitutive N-myc overexpression as a model system. Overall, the capacity of these cells to differentitate morphologically in response to various differentiation protocols was retained, thus offering an explanation to the lack of correlation between N-myc expression and patient outcome in non-N-myc-amplified tumors.
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| 22. |
- Dewyngaert, J. Keith, et al.
(författare)
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Procedure for unmasking localization information from ProstaScint scans for prostate radiation therapy treatment planning
- 2004
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Ingår i: International Journal of Radiation Oncology, Biology, Physics. - : Elsevier BV. - 0360-3016 .- 1879-355X. ; 60:2, s. 654-662
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: To demonstrate a method to extract the meaningful biologic information from In-111-radiolabeled capromab pendetide (ProstaScint) SPECT scans for use in radiation therapy treatment planning by removing that component of the In-111 SPECT images associated with normal structures. Methods and Materials: We examined 20 of more than 80 patients who underwent simultaneous Tc-99m/In-111 SPECT scans, which were subsequently registered to the corresponding CT/MRI scans. A thresholding algorithm was used to identify Tc-99m uptake associated with blood vessels and CT electron density associated with bone marrow. Corresponding voxels were removed from the In-111 image set. Results: No single threshold value was found to be associated with the Tc-99m uptake that corresponded to the blood vessels. Intensity values were normalized to a global maximum and, as such, were dependent upon the quantity of Tc-99m pooled in the bladder. The reduced ProstaScint volume sets were segmented by use of a thresholding feature of the planning system and superimposed on the CT/MRI scans. Conclusions: ProstaScint images are now closer to becoming a biologically and therapeutically useful and accurate image set. After known sources of normal intensity are stripped away, the remaining areas that demonstrate uptake may be segmented and superimposed on the treatment-planning CT/MRI volume.
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| 23. |
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| 24. |
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| 25. |
- Brun, Eva
(författare)
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Head and Neck Cancer: Studies on microvessel density, radiation response and FDG PET
- 2001
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Treatment options of head and neck squamous cell carcinoma (HNSCC) usually include combinations of radiotherapy and surgery, and in some cases addition of chemotherapy. In locally advanced cases cure rates are low. Current prognostic factors cannot foresee the outcome for the individual patient. There is consequently a need for reliable prognostic and predictive factors. Through identification of such factors therapeutic interventions can be made early during therapy to increase tumour control and survival. In the present studies the association between microvessel density (MVD) in tumours and response to radiation has been explored. We have also studied the association between response to radiation and tumour metabolism, both prior to and during therapy (radical radiotherapy and in 10 cases also neoadjuvant chemotherapy). Metabolism was studied with a glucose analogue, FDG, and positron emission tomography, PET.The metabolic rate of FDG was compared to treatment outcome and survival and also to established tumour properties, as cell proliferation, tumourgrade and DNAcontent. Microvessel density showed a complex relation to radiation treatment response and outcome. Among patients with tumours manifesting complete response to radiotherapy MVD was above the lowest quartile of the MVDcounts according to computerised image analysis. In the subsequent study the relationship between higher MVD and response to radiotherapy could not be reproduced, when performed manually. High MVD within the epithelial tumour tissue, not in the tumour stroma, was then found to be an adverse prognostic factor, with a lower probability of local control and a higher rate of distant metastases.Tumour response evaluated histopathologically, after a preoperative radiation dose of 50 Gy was strongly correlated to outcome, regardless of the subsequent radical surgery.This implies that radiosensitivity per se is a strong prognostic marker. Tumour metabolism (FDG PET) was associated to therapy outcome. The pre treatment value was of limited prognostic value whereas the second PET, early during therapy, was associated to therapy outcome, in terms of complete response, local control and survival. When comparing the value of the metabolic rate (MR) to a simpler quantification, the standar-dised uptake value (SUV) of FDG, we found that MR was more strongly correlated to therapy outcome. Furthermore associations were found to be significant only for the primary tumours and not for node metastases. This implies a different pattern of response in node metastases compared to that of the corresponding primary tumour. There was no strong association between tumour metabolism and proliferation, DNA content or histologic grade. MR FDG reflects tumour aggressiveness. Repeated FDG studies during therapy are feasible and might justify therapeutic interventions in non-responders.
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| 26. |
- Molin, Daniel, 1969-
(författare)
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Bystander Cells and Prognosis in Hodgkin Lymphoma
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Hodgkin lymphoma (HL) is characterised histologically by a minority of malignant Hodgkin and Reed-Sternberg (HRS) cells surrounded by benign cells, and clinically by a relatively good prognosis. The treatment, however, leads to a risk of serious side effects. Knowledge about the biology of the disease, particularly the interaction between the HRS cells and the surrounding cells, is essential in order to improve diagnosis and treatment. HL patients with abundant eosinophils in the tumours have a poor prognosis, therefore the eosinophil derived protein eosinophil cationic protein (ECP) was studied. Serum-ECP (S-ECP) was elevated in most HL patients. It correlated to number of tumour eosinophils, nodular sclerosis (NS) histology, and the negative prognostic factors high erythrocyte sedimentation rate (ESR) and blood leukocyte count (WBC). A polymorphism in the ECP gene (434(G>C)) was identified and the 434GG genotype correlated to NS histology and high ESR.The poor prognosis in patients with abundant eosinophils in the tumours has been proposed to depend on HRS cell stimulation by the eosinophils via a CD30 ligand (CD30L)-CD30 interaction. However, CD30L mRNA and protein were detected in mast cells and the predominant CD30L expressing cell in HL is the mast cell. Mast cells were shown to stimulate HRS cell lines via CD30L-CD30 interaction. The number of mast cells in HL tumours correlated to worse relapse-free survival, NS histology, high WBC, and low blood haemoglobin. Survival in patients with early and intermediate stage HL, diagnosed between 1985 and 1992, was generally favourable and comparatively limited treatment was sufficient to produce acceptable results for most stages. The majority of relapses could be salvaged. Patients treated with a short course of chemotherapy and radiotherapy had an excellent outcome.In conclusion prognosis is favourable in early and intermediate stages and there are possibilities for further improvements based on the fact that mast cells and eosinophils affect the biology and prognosis of HL.
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| 27. |
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| 29. |
- Dahlin, Lars, et al.
(författare)
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Granular cell tumour of the ulnar nerve in a young adult.
- 2002
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Ingår i: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 36:1, s. 46-49
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Tidskriftsartikel (refereegranskat)
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| 30. |
- Tsuda, S, et al.
(författare)
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Flat and depressed colorectal tumours in a southern Swedish population: a prospective chromoendoscopic and histopathological study.0
- 2002
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Ingår i: Gut. - : BMJ. - 1468-3288 .- 0017-5749. ; 51:4, s. 550-555
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Tidskriftsartikel (refereegranskat)abstract
- Background: Flat and depressed colorectal tumours are common in Japan but are very rare or non-existent in Western countries. Aims: To study the occurrence of flat colorectal tumours in a southern Swedish population. Methods: In this prospective study, 371 consecutive European patients were examined by high resolution video colonoscopy combined with chromoendoscopy. The nature of the lesions was determined by histopathological examination. Results: A total of 973 tumours were found; 907 (93.2%) were protruding and 66 (6.8%) were flat or depressed. Of the flat/depressed tumours, five (7.7%) were early adenocarcinomas infiltrating the submucosa. Eleven carcinomas (1.2%) were found among protruding tumours. High grade dysplasia was observed in 18% (n=11) of flat/depressed adenomas in contrast with 7.3% (n=65) of protruding adenomas, and occurred in smaller flat/depressed tumours compared with protruding ones (mean diameter 8 mm v 23 mm, respectively). Furthermore, high grade dysplasia was significantly more common in flat elevated tumours with central depression or in depressed adenomas (35.7%; 5/14) than in flat elevated adenomas (12.8%; 6/47). Conclusion: Flat and depressed tumours exist in a Western population. Future studies should address whether or not chromoendoscopy with video colonoscopy is necessary in the search for flat colorectal neoplasms.
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