Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Cancer och onkologi) srt2:(2000-2004)"

Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Cancer och onkologi) > (2000-2004)

Sortera/gruppera träfflistan
  • Alvarado-Kristensson, Maria, et al. (författare)
  • p38-MAPK Signals Survival by Phosphorylation of Caspase-8 and Caspase-3 in Human Neutrophils.
  • 2004
  • Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 1540-9538 .- 0022-1007. ; 199:4, s. 449-458
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutrophil apoptosis occurs both in the bloodstream and in the tissue and is considered essential for the resolution of an inflammatory process. Here, we show that p38–mitogen-activated protein kinase (MAPK) associates to caspase-8 and caspase-3 during neutrophil apoptosis and that p38-MAPK activity, previously shown to be a survival signal in these primary cells, correlates with the levels of caspase-8 and caspase-3 phosphorylation. In in vitro experiments, immunoprecipitated active p38-MAPK phosphorylated and inhibited the activity of the active p20 subunits of caspase-8 and caspase-3. Phosphopeptide mapping revealed that these phosphorylations occurred on serine-364 and serine-150, respectively. Introduction of mutated (S150A), but not wild-type, TAT-tagged caspase-3 into primary neutrophils made the Fas-induced apoptotic response insensitive to p38-MAPK inhibition. Consequently, p38-MAPK can directly phosphorylate and inhibit the activities of caspase-8 and caspase-3 and thereby hinder neutrophil apoptosis, and, in so doing, regulate the inflammatory response. This research was originally published in The Journal of Experimental Medicine.
  • Alvarado-Kristensson, Maria, et al. (författare)
  • p38 Mitogen-activated protein kinase and phosphatidylinositol 3-kinase activities have opposite effects on human neutrophil apoptosis.
  • 2002
  • Ingår i: FASEB Journal. - : The Federation of American Societies for Experimental Biology. - 1530-6860. ; 16:1, s. 31-129
  • Tidskriftsartikel (refereegranskat)abstract
    • Neutrophil apoptosis is essential for resolution of inflammatory reactions. Here, we studied the role of two apoptosis/survival-associated protein kinases in this process. We discovered a previously undetected early and transient inhibition of the activity of p38 mitogen-activated protein kinase (p38 MAPK) during both spontaneous and Fas-induced apoptosis. Pharmacological inhibition of this enzyme augmented the activation of caspases and the apoptotic response, which suggests that the p38 MAPK signals survival in neutrophils. Our finding that caspase-3 activity was initiated during the transient inhibition of p38 MAPK suggests that apoptosis is initiated during this inhibition. Furthermore, such transient inhibition was counteracted by granulocyte-macrophage colony-stimulating factor, which elicits survival. We also found that neither this inhibition of p38 MAPK nor the spontaneous apoptotic response depended on Fas. Instead, the early inhibition of p38 MAPK concurred with a Fas-induced activation of phosphatidylinositol 3-kinase, inhibition of which reduced apoptosis. Thus, the Fas-induced augmentation of spontaneous apoptosis can be explained by its activation of phosphatidylinositol 3-kinase. We conclude that p38 MAPK activity represents a survival signal that is inactivated transiently during both spontaneous and Fas-induced apoptosis, whereas Fas-induced phosphatidylinositol 3-kinase activity is a proapoptotic signal in isolated human neutrophils.
  • Alvarado-Kristensson, Maria (författare)
  • Regulation of neutrophil apoptosis
  • 2004
  • Doktorsavhandling (övrigt vetenskapligt)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.
  • Amini, Rose-Marie, 1969- (författare)
  • Hodgkin Lymphoma : Studies of Advanced Stages, Relapses and the Relation to Non-Hodgkin Lymphomas
  • 2002
  • Doktorsavhandling (övrigt vetenskapligt)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.
  • Andersson, Anna, et al. (författare)
  • Paired multiplex reverse-transcriptase polymerase chain reaction (PMRT-PCR) analysis as a rapid and accurate diagnostic tool for the detection of MLL fusion genes in hematologic malignancies
  • 2001
  • Ingår i: Leukemia. - : Nature Publishing Group. - 1476-5551. ; 15:8, s. 1293-1293
  • Tidskriftsartikel (refereegranskat)abstract
    • The MLL gene in chromosome band 11q23 is frequently rearranged in acute lymphoblastic and acute myeloid leukemias. To date, more than 50 different chromosomal regions are known to participate in translocations involving 11q23, many of which affect MLL. The pathogenetically important outcome of these rearrangements is most likely the creation of a fusion gene consisting of the 5' part of the MLL gene and the 3' end of the partner gene. Although abnormalities of the MLL gene as such are generally associated with poor survival, recent data suggest that the prognostic impact varies among the different fusion genes generated. Hence, detection of the specific chimeric gene produced is important for proper prognostication and clinical decision making. We have developed a paired multiplex reverse-transcriptase polymerase chain reaction analysis to facilitate a rapid and accurate detection of the most frequent MLL fusion genes in adult and childhood acute leukemias. To increase the specificity, two sets of primers were designed for each fusion gene, and these paired primer sets were run in parallel in two separate multiplex one-step PCR reactions. Using the described protocol, we were able to amplify successfully, in one single assay, the six clinically relevant fusion genes generated by the t(4;11)(q21;q23) [MLL/AF4], t(6;11)(q27;q23) [MLL/AF6], t(9;11)(p21-22;q23) [MLL/AF9], t(10;11)(p11-13;q23) [MLL/AF10], t(11;19)(q23;p13.1) [MLL/ELL], and t(11;19)(q23; p13.3) [MLL/ENL] in cell lines, as well as in patient material.
  • Andersson-Engels, Stefan, et al. (författare)
  • Integrated system for interstitial photodynamic therapy
  • 2003
  • Ingår i: Therapeutic Laser Applications and Laser-Tissue Interactions,Munich, Germany,2003-06-24 - 2003-06-25. - : The International Society for Optical Engineering. ; 5142, s. 42-49
  • Konferensbidrag (refereegranskat)abstract
    • A novel photodynamic therapy system based on interstitial illumination using multiple fibres is under development. The aim with this system is to enable treatment of large tumour volumes and also to utilise real-time measurements to allow on-line dosimetry. Important dosimetric parameters to measure are light fluence rate, sensitizer fluorescence intensity and local blood oxygenation. A construction which allows all functions to be readily performed with a single system is presented. We believe that interstitial PDT utilising this technique may be attractive in many clinical situations.
  • Andersson-Engels, Stefan, et al. (författare)
  • Integrated system for interstitial photodynamic therapy
  • 2002
  • Ingår i: Conference on Advanced Optical Devices, Technologies, and Medical Applications,Riga, Latvia,2002-08-19 - 2002-08-22. - : The International Society for Optical Engineering. ; 5123, s. 293-302
  • Konferensbidrag (refereegranskat)abstract
    • To develop PDT beyond treatment of thin superficial tumours, to also be an efficient treatment alternative for deeply located and/or thick tumours, a system based on interstitial illumination using multiple fibres has been developed. Conditions that could benefit from such a treatment modality are for instance malignant brain tumours and tumours in the oral cavity. In interstitial PDT one needs to use multiple fibres for light delivery in order to allow treatments of tumours larger than a few millimetres in diameter. Our system consists of a laser light source, a beam-splitting system dividing the light into three or six output fibres and a custom-made dosimetry programme. The concept is then to use these fibres not only for delivering the treatment light but also to measure parameters of interest for the treatment outcome. The fluence rate of the light emitted by each fibre is measured at the positions of the other fibre tips. From these results the light dose at all positions could be recalculated. Changes in optical properties as well as bleaching and concentration of the photosensitizer during the treatment could be monitored and compensated for in the dosimetry. Tumours have been treated both in experimental studies and in patients with thick superficial Basal Cell Carcinomas. Almost all treated skin lesions responded with complete response.
Skapa referenser, mejla, bekava och länka
Typ av publikation
tidskriftsartikel (682)
doktorsavhandling (72)
forskningsöversikt (17)
konferensbidrag (15)
bokkapitel (10)
rapport (1)
visa fler...
annan publikation (1)
visa färre...
Typ av innehåll
refereegranskat (674)
övrigt vetenskapligt (123)
populärvet., debatt m.m. (1)
Borg, Åke (38)
Olsson, Håkan (36)
Fernö, Mårten (30)
Bendahl, Pär Ola (25)
Möller, Torgil (24)
Glimelius, B (23)
visa fler...
Mertens, Fredrik (21)
Berglund, Göran (21)
Nilbert, Mef (21)
Landberg, Göran (19)
Glimelius, Bengt (18)
Larsson, Christer (18)
Baldetorp, Bo (18)
Påhlman, Sven (17)
Anderson, Harald (17)
Tennvall, Jan (16)
Dasu, Alexandru (16)
Domanski, Henryk (16)
Dillner, J (15)
Dillner, Joakim (15)
Åkerman, Måns (15)
Alvegård, Thor (14)
Axelson, Håkan (13)
Strand, Sven-Erik (13)
Blomqvist, Carl (12)
Svanberg, Katarina (12)
Ringnér, Markus (12)
Karlsson, Mats G, 19 ... (12)
Toma-Dasu, Iuliana (12)
Manjer, Jonas (11)
Wolk, A (11)
Mitelman, Felix (11)
Stenram, Unne (10)
Mattsson, Sören (10)
Hallmans, Göran (10)
Hallmans, G (10)
Albertsson, Maria (10)
Härkönen, Pirkko (10)
Roos, G (10)
Rydholm, Anders (10)
Janzon, Lars (10)
Loman, Niklas (10)
Jernström, Helena (10)
Lenner, Per (9)
Svanberg, Sune (9)
Johansson, Bertil (9)
Gustafson, Pelle (9)
Garwicz, Stanislaw (9)
Willen, R. (9)
Dictor, Michael (9)
visa färre...
Lunds universitet (618)
Karolinska Institutet (107)
Uppsala universitet (90)
Umeå universitet (57)
Linköpings universitet (37)
Örebro universitet (29)
visa fler...
Stockholms universitet (9)
Göteborgs universitet (5)
Jönköping University (5)
Södertörns högskola (4)
Malmö universitet (2)
Högskolan i Halmstad (2)
Linnéuniversitetet (2)
Ersta Sköndal Bräcke högskola (2)
Högskolan i Gävle (1)
Blekinge Tekniska Högskola (1)
visa färre...
Engelska (785)
Svenska (11)
Kinesiska (1)
Annat språk (1)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (798)
Naturvetenskap (6)
Samhällsvetenskap (1)


pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy