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- Räihä, Niels, et al.
(författare)
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Letters to the editor.
- 2004
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Ingår i: Journal of Pediatric Gastroenterology and Nutrition - Jpgn. - : Elsevier BV. - 1536-4801. ; 18:4, s. 453-453
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Andersson, Håkan, 1944
(författare)
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Radioimmunotherapy of experimental ovarian cancer with Astatine-211. An in vivo model for consolidation treatment in women
- 2000
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- About 850 new cases of ovarian cancer are diagnosed in Sweden every year. In 75 % of the patients the tumour has spread outside the ovaries. The standard treatment is surgery followed by six courses of combination chemotherapy. In spite of a very high frequency of clinical complete responses the 5-year survival is not satisfactory. Thus there is a great need for consolidating therapy.Radioimmunotherapy (RIT), i.e. treatment with specific monoclonal antibodies (MAb) labelled with radionuclides has been tried for various tumours experimentally and clinically. In most studies b-emitters have been used but for micrometastases an a-emitter with a very short tissue range may be better.The purpose of this study was to examine the in vitro effect of the a-emitter Astatine-211 (211At) and to investigate the therapeutic efficacy of regional administration of the specific antibody MOv18 labelled with 211At to nude mice with intraperitoneal growth of human ovarian cancer. Methods. For the in vitro studies the two human cancer cell lines NIH:OVCAR-3 and Colo-205 were used. Cell suspensions were treated with free 211At, 211At-albumin, 211At-Mab or with photon irradiation. The human ovarian cancer cell line NIH:OVCAR-3 was used for the in vivo studies. Two weeks after the inoculation of cells, when the tumour still was microscopic, 211At-MOv18 was injected intraperitoneally. The therapeutic effect was evaluated six weeks later except in the long-term studyResults. In vitro the uptake of free 211At on both cell lines was unexpectedly high. A low number (19-31) of 211At decays on the cell surface was needed for 37% cell survival for both cell types.In the short term in vivo studies 18 of 20 mice were tumour-free when 211At-MOv18 was injected i.p. In the long-term study the survival was significantly better for treated than for untreated mice. Thirty-three per cent of the animals were tumour-free at the end of the study.Conclusion. Intraperitoneal radioimmunotherapy with an 211At-labelled specific antibody is an effective treatment of human ovarian cancer growing in nude mice. Hopefully, this treatment will be of value as consolidating treatment in women with minimal residual disease after surgery and chemotherapy
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- Terstappen, Karin, 1967
(författare)
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Pigmentierte basalzellkarzinome.
- 2003
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Ingår i: Dermatoskopie von Hauttumoren.. - Darmstadt, Tyskland : Steinkopff Verlag.
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Ahlgren, Johan, 1960-
(författare)
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Studies on Prediction of Axillary Lymph Node Status in Invasive Breast Cancer
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common malignancy among females in Sweden. Axillary lymph-node dissection is a standard procedure in the management of breast cancer, aiming at obtaining prognostic information for adjuvant therapy decisions. Axillary dissection entails considerable morbidity. The aims of this study were to establish more selective surgical approaches and to investigate angiogenesis, a potential predictor for lymph-node metastases and prognosis.Clinical nodal status, tumour size and S-phase were associated with nodal metastases in cohort of 1145 women. The proportion of nodal metastases was 13% in the subgroup with the lowest risk.In a study from two registries, 675 and 1035 breast cancers ≤10 mm diagnosed by screening mammography had nodal metastases in 6,5% and 7%, respectively. Clinically detected cancers had a risk of 16% and 14%, respectively.In a study on 415 women, a 5-node biopsy of the axilla had a sensitivity of 97,3% and a false negative rate of 2,7% in comparison with axillary dissection.Six sections from 21 breast cancers were analysed for microvessel density (MVD). The inter-section variation contributed more to the total variance than inter-tumour variation, 45,0% and 37,3%, respectively.In a cohort of 315 women, breast cancers with high MVD more frequently had p53 mutations (27,1%) compared with cases with low MVD (18,4%). This difference was not statistically significant (p=0,075). p53 mutations were associated with a worse outcome, whereas MVD was not.In conclusion, women with screening detected ≤10 mm breast cancers have a low risk of lymph node metastases and some may not need axillary dissection in the future. The 5-node biopsy could be an alternative to axillary dissection. MVD is associated with methodological weaknesses and routine use is not recommended.
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| 8. |
- Alvarado-Kristensson, Maria
(författare)
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Regulation of neutrophil apoptosis
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The human neutrophil is the most abundant granulocyte and the major type of cell involved in an acute inflammatory response. Neutrophils are armed with various systems of enzymes, that can find and kill pathogens, but unfortunately, these "weapons" cannot distinguish between the host tissues and the "invaders." Therefore, an extensive neutrophil reaction leads to continuous release of toxic metabolites, which causes successive self-destruction of host tissues and possibly also organ failure. Such a series of destructive events has been implicated in diseases such as rheumatoid arthritis, myocardial infarction/reperfusion injury, atherogenesis, asthma, cystic fibrosis, emphysema, and vasculitis. Resolution of an acute inflammatory process depends on termination of neutrophil emigration from blood vessels and clearance of extravasated neutrophils and their metabolic products. Outside the blood vessels, neutrophils spontaneously undergo apoptosis, and are therefore removed by phagocytic cells at the site of inflammation. Neutrophil apoptosis can be modulated by several factors in the local environment, such as the Fas ligand (FasL), but the molecular mechanisms involved are poorly understood. In this dissertation thesis, I describe and elucidate intracellular signalling mechanisms that are involved in regulation of spontaneous and Fas-induced apoptosis in human neutrophils. Using two different methods it was possible to detect constitutive activity of p38 mitogen-activated protein kinase (p38) in newly isolated neutrophils. The p38 survival signal was transiently lost during both spontaneous and Fas-induced apoptosis, favoured induction of the apoptotic process. During the transient loss of p38 activity there was a temporary Fas-induced increase in phosphatidylinositol 3-kinase (PI3K) activity, which also had a pro-apoptotic impact on the neutrophils. In addition, my experiments showed that the active form of p38 associates with caspase 8 and caspase 3, which is necessary for p38-induced phosphorylation of serine-362 and serine-150 on these caspases. These biochemical modifications impair the activities, and possibly also the stability, of caspase 8 and 3 and thereby weaken the capacity of these enzymes to induce apoptosis. The results in this dissertation also demonstrate that the protein phosphatase type 2A (PP2A) can directly and independently decrease the phosphorylation levels of both p38 and caspase 3. Consequently, PP2A can increase the activity of caspase 3 by dual mechanisms and thereby promote the apoptotic response in human neutrophils.
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| 9. |
- Amini, Rose-Marie, 1969-
(författare)
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Hodgkin Lymphoma : Studies of Advanced Stages, Relapses and the Relation to Non-Hodgkin Lymphomas
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The relationship between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) is not entirely elucidated and a clonal relation may be present more often than previously believed. Mechanisms of tumour progression and resistance to therapy are poorly understood.Between 1974 and 1994 all individuals in Sweden with both HL and NHL were identified. Thirty-two cases were studied using clinical, histopathological and immunohistochemical methods. The second lymphoma often appeared in an aggressive clinical form and a significant correlation between the expression of p53 and LMP-1 in the first and second lymphoma was demonstrated.The treatment outcome for 307 patients with advanced stages of HL, in an unselected population was in accordance with the treatment results of large centres world-wide. Some patients were successfully selected for a shorter chemotherapy-regimen without inferior treatment results.In 124 patients with relapse, the survival of those primarily treated with radiotherapy according to the National guidelines was in accordance with the survival of patients of initially advanced stages. A worse outcome was found for those who received both chemotherapy and radiotherapy initially, probably because of a higher frequency of bulky disease in this group. Immunohistochemical analysis of the tumour suppressor protein p53 and retinoblastoma protein (Rb) of paired samples at diagnosis and at relapse in 81 patients did not reveal any specific staining pattern affecting survival.A novel B-cell line (U-2932) was established from a patient with a diffuse large B-cell lymphoma previously treated for advanced stage and subsequent relapses of HL. An identical rearranged IgH gene was demonstrated in tumour cells from the patient and in U-2932. A p53 point mutation was detected and over-expression of the p53 protein was found. A complex karyotype with high-level amplifications of the chromosomal regions 18q21 and 3q27, i.e. the loci for bcl-2 and bcl-6 were demonstrated.
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