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Träfflista för sökning "hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Cancer och onkologi) srt2:(2000-2004);srt2:(2003)"

Sökning: hsv:(MEDICIN OCH HÄLSOVETENSKAP) hsv:(Klinisk medicin) hsv:(Cancer och onkologi) > (2000-2004) > (2003)

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  • Aus, Gunnar, et al. (författare)
  • Prognostic Factors and Survival in Node-Positive (N1) Prostate Cancer : A Prospective Study Based on Data from a Swedish Population-Based Cohort
  • 2003
  • Ingår i: European Urology. - 0302-2838 .- 1873-7560. ; 43:6, s. 627-631
  • Tidskriftsartikel (refereegranskat)abstract
    • <p><strong><em>Objective:</em></strong> At presentation of prostate cancer, patients with proven lymph node metastasis (N1) are comparatively rare. It is difficult to give prognostic information based on the present literature. The aim of this study was to evaluate the impact of known risk factors in patients with pelvic node involvement and without distant metastasis.</p> <p><strong><em>Methods:</em></strong> From the population-based, prospective prostate cancer tumour registry of the South–East Region in Sweden, we collected data on all 181 patients with N1, M0 prostate cancer diagnosed from January 1987 to October 2000 with a follow-up to December 2001. Mean follow-up was 62 months. Pre-operative risk factors as age, T-category, serum PSA, tumour grade and also primary treatment given was correlated to the outcome.</p> <p><strong><em>Results:</em></strong> Median age at diagnosis was 65 years. Cancer-specific survival was highly variable with 5-year survival of 72%, a median of 8 years and the projected 13-year figure was 31%. T-category, age, PSA or treatment did not affect the outcome while poorly differentiated tumours had a tendency towards lower cancer-specific survival (<em>p</em>=0.0523) when compared to well and moderately differentiated tumours.</p> <p><strong><em>Conclusions:</em></strong> This population-based cohort of prostate cancer patients with pelvic node involvement treated principally with non-curative intent had a median cancer-specific survival of 8 years. Preoperatively known risk factors seem to have but a modest impact on the prognosis for patients in this stage of the disease.</p>
  • Baldetorp, Bo, et al. (författare)
  • Improved DNA flow cytometric, DNA ploidy, and S-phase reproducibility between 15 laboratories in analysis of breast cancer using generalized guidelines
  • 2003
  • Ingår i: Cytometry. - John Wiley and Sons Inc.. - 0196-4763. ; 56A:1, s. 1-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Lack of generalized guidelines for DNA flow cytometric analysis (FCM) may be the main reason for its limited use in the clinical management of breast cancer. Methods: After an initial interlaboratory reproducibility study (Round 1), we concluded that it was the evaluation of the DNA histograms rather than the technical performance of the analysis that was the main reason for discordant results between laboratories. Guidelines for the interpretation of DNA histograms were therefore drawn up. We present here data from a new reproducibility study (Round 11) using these guidelines. Results: For 10 laboratories also participating in Round 1, use of the guidelines increased the concordance in DNA ploidy status from 89% to 100% for the 46 samples used in both rounds. The concordance rate for SPF also increased; mean r(s)-value increased from 0.81 to 0.88, and mean kappa value (lower two-thirds versus upper third versus not reported) increased from 0.55 to 0.71. Five new laboratories, participating only in Round II, also agreed with the 10 original laboratories regarding DNA ploidy status. With the inclusion of all 15 laboratories, we obtained a mean r(s)-value of 0.81 and a mean kappa value of 0.72 for SPF. Conclusions: Generalized guidelines for DNA FCM increase interlaboratory agreement, which is highly important in clinical routines and in multicenter studies. Furthermore, inexperienced FCM laboratories using generalized guidelines can produce and interpret DNA FCM data equally as well as experienced laboratories. Cytometry Part A 56A:1-7, 2003. (C) 2003 Wiley-Liss, Inc.
  • Baust, H., et al. (författare)
  • Evidence for radiosensitizing by gliotoxin in HL-60 cells implications for a role of NF-kappa B independent mechanisms
  • 2003
  • Ingår i: Oncogene. - 0950-9232 .- 1476-5594. ; 22:54, s. 8786-8796
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Radioresistance markedly impairs the efficacy of tumor radiotherapy and may involve antiapoptotic signal transduction pathways that prevent radiation-induced cell death. A common cellular response to genotoxic stress induced by radiation is the activation of the nuclear factor kappa B (NF-kappaB). NF-kappaB activation in turn can lead to an inhibition of radiation-induced apoptotic cell death. Thus, inhibition of NF-kappaB activation is commonly regarded as an important strategy to abolish radioresistance. Among other compounds, the fungal metabolite gliotoxin (GT) has been reported to be a highly selective inhibitor of NF-kappaB activation. Indeed, low doses of GT were sufficient to significantly enhance radiation-induced apoptosis in HL-60 cells. However, this effect turned out to be largely independent of NF-kappaB activation since radiation of HL-60 cells with clinically relevant doses of radiation induced only a marginal increase in NF-kappaB activity, and selective inhibition of NF-kappaB by SN50 did not result in a marked enhancement of GT-induced apoptosis. GT induced activation of JNKs, cytochrome c release from the mitochondria and potently stimulated the caspase cascade inducing cleavage of caspases -9, -8, -7 and -3. Furthermore, cleavage of the antiapoptotic protein X-linked IAP and downregulation of the G2/M-specific IAP-family member survivin were observed during GT-induced apoptosis. Finally, the radiation-induced G2/M arrest was markedly reduced in GT-treated cells most likely due to the rapid induction of apoptosis. Our data demonstrate that various other pathways apart from the NF-kappaB signaling complex can sensitize tumor cells to radiation and propose a novel mechanism for radio-sensitization by GT, the interference with the G2/M checkpoint that is important for repair of radiation-induced DNA damage in p53-deficient tumor cells.</p>
  • Belting, Mattias (författare)
  • Heparan sulfate proteoglycan as a plasma membrane carrier
  • 2003
  • Ingår i: Trends in Biochemical Sciences. - Elsevier. - 0167-7640. ; 28:3, s. 145-151
  • Tidskriftsartikel (refereegranskat)abstract
    • The plasma membrane defines the border of living cells and provides a barrier to extracellular components. Advances in molecular biology have resulted in the development of novel therapeutic strategies (e.g. gene therapy and cellular protein delivery) which rely on the entry of charged macromolecules into the intracellular compartment. Recent reports demonstrate an intriguing role for heparan sulfate proteoglycans in cellular internalization of viruses, basic peptides and polycation-nucleic-acid complexes and the possibility that they have important implications for gene transfer and protein delivery to mammalian cells. This review focuses on heparan sulfate proteoglycan as a plasma membrane carrier.
  • Berg, G, et al. (författare)
  • A systematic overview of radiation therapy effects in brain tumours.
  • 2003
  • Ingår i: Acta oncologica (Stockholm, Sweden). - 0284-186X. ; 42:5-6, s. 582-8
  • Tidskriftsartikel (refereegranskat)abstract
    • A systematic review of radiation therapy trials in several tumour types was performed by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for brain turnouts is based on data from 9 randomized trials and 1 meta-analysis. Moreover, data from 2 prospective studies, 3 retrospective studies and 4 other articles were used. In total, 19 scientific articles are included, involving 4266 patients. The results were compared with those of a similar overview from 1996 including 11252 patients. The conclusions reached can be summarized as follows: The conclusion from SBU 129/2 that curative treatment is not available for patients with high-grade malignant glioma (grade III and IV) is still valid. The survival benefit from postoperative radiotherapy compared to supportive care only or chemotherapy is about 3-4 months, as demonstrated in earlier randomized studies. Quality of life is now currently estimated and considered to be of major importance when reporting the outcome of treatment for patients with brain tumours. There is no scientific evidence that radiotherapy using hyper- and hypofractionation leads to longer survival for patients with high-grade malignant glioma than conventional radiotherapy There is large documentation, but only one randomized study. There is some documentation to support the view that patients with grade IV glioma and poor prognosis can be treated with hypofractionation and with an outcome similar to that after conventional fractionation. A shorter treatment time should be convenient for the patient. Documentation of the benefit of a radiotherapy boost with brachytherapy is limited and no conclusion can be drawn. There is no scientific evidence that radiotherapy prolongs life for patients with low-grade glioma. There are some data supporting that radiotherapy can be used to treat symptoms in patients with low-grade glioma. As no controlled studies have been reported, no firm conclusion can be drawn.
  • Blind, Per-Jonas, et al. (författare)
  • Unique antitumour effects of L-2,4 diaminobutyric acid on cultured hepatoma cells
  • 2003
  • Ingår i: Anticancer research. - International Institute of Cancer Research. - 1791-7530. ; 23:2B, s. 1245-1248
  • Tidskriftsartikel (refereegranskat)abstract
    • A single hepatoma cell line was grown in vitro and incubated with L-2,4 diaminobutyric acid (DAB), a non-metabolizable amino acid, under various conditions. The tumour cells were irreversibly damaged by incubation for 8 hours with 8 mmol/L of DAB. The tumour cell-destroying effect of DAB was dose- and time-dependent with no effect at a DAB concentration of 1.6 mmol/L. The presence of N-methyl a-aminoisobutyric acid (a specific substrate of amino acid transport system A) in the incubation medium abrogated the tumour cell destructive effect of DAB in a dose- dependent fashion. The presence of it on-physiological amino acids in the incubation medium per se was not the cause of tumour cell destruction, since inclusion of a-amino-isobutyric acid and N-methyl a-aminoisobutyric acid in the incubation medium did not influence the viability of hepatoma cells. We conclude that the tumour cell destructive effect of DAB was the result of a huge and unlimited uptake of DAB energized by the Na+-gradient and that this uptake was not subjected to the law of saturation kinetics. This was combined with a tumour cell energy crisis in attempts to restore the Na+-gradient.
  • Bolcato-Bellemin, AL, et al. (författare)
  • Laminin alpha 5 chain is required for intestinal smooth muscle development
  • 2003
  • Ingår i: Developmental Biology. - Elsevier. - 1095-564X. ; 260:2, s. 376-390
  • Tidskriftsartikel (refereegranskat)abstract
    • Laminins (comprised of alpha, beta, and gamma chains) are heterotrimeric glycoproteins integral to all basement membranes. The function of the lammin alpha5 chain in the developing intestine was defined by analysing laminin alpha5(-/-) mutants and by grafting experiments. We show that lammin alpha5 plays a major role in smooth muscle organisation and differentiation, as excessive folding of intestinal loops and delay in the expression of specific markers are observed in laminin alpha5(-/-) mice. In the subepithelial basement membrane, loss of alpha5 expression was paralleled by ectopic or accelerated deposition of laminin alpha2 and alpha4 chains; this may explain why no obvious defects were observed in the villous form and enterocytic differentiation. This compensation process is attributable to mesenchyme-derived molecules as assessed by chick/mouse alpha5(-/-) grafted associations. Lack of the laminin alpha5 chain was accompanied by a decrease in epithelial alpha3beta1 integrin receptor expression adjacent to the epithelia] basement membrane and of Lutheran blood group glycoprotein in the smooth muscle cells, indicating that these receptors are likely mediating interactions with laminin alpha5-containing molecules. Taken together, the data indicate that the laminin alpha5 chain is essential for normal development of the intestinal smooth muscle and point to possible mesenchyme-derived compensation to promote normal intestinal morphogenesis when laminin alpha5 is absent. (C) 2003 Elsevier Science (USA). All rights reserved.
  • Borg, Åke, et al. (författare)
  • Predicting the future of breast cancer.
  • 2003
  • Ingår i: Nature Medicine. - Nature Publishing Group. - 1546-170X. ; 9:1, s. 16-18
  • Tidskriftsartikel (refereegranskat)
  • Borgfeldt, Christer, et al. (författare)
  • High tumor tissue concentration of urokinase plasminogen activator receptor is associated with good prognosis in patients with ovarian cancer
  • 2003
  • Ingår i: International Journal of Cancer. - John Wiley and Sons Inc.. - 0020-7136. ; 107:4, s. 658-665
  • Tidskriftsartikel (refereegranskat)abstract
    • volved in tumor growth and metastasis. We assayed the components of the uPA system in homogenates of 64 primary epithelial ovarian tumors and 5 metastases and evaluated the association of these parameters to prognosis in the 51 malignant cases. The levels of uPA, PAI-2 and the uPA: PAI-I complex increased with progressive loss of histological differentiation (P-trend <0.001, <0.05 and <0.001). The level of PAI-I was higher in poorly than in well/moderately differentiated tumors (p = 0.03). The content of uPAR was lower in benign tumors as compared to borderline malignancies (p = 0.002), invasive primary tumors (p < 0.001), and metastases (p = 0.002). Surprisingly, the level of uPAR was lower in poorly differentiated as compared to both borderline (p = 0.01) and well differentiated malignant tumors (p = 0.005). Also, the level of uPAR was lower in advanced as compared to early stages of the disease (P-trend = 0.002). The median follow-up time for patients was 5.8 years. High tumor tissue levels of uPAR were associated with longer postoperative survival (HR = 0.4, 95% CI = 0.2-0.8, p = 0.01). In contrast, shorter survival was evident in patients with high tumor levels of uPA from 2 years on after operation (HR = 4.6, 95% CI = 1.2-17, p = 0.02). High tPA levels tended to be associated with shorter overall survival after 2 years (HR = 2.9, 95% 95% Cl = 0.9-9.8, p = 0.08). Although high tumor tissue content of uPAR was associated with a less aggressive phenotype characterized by well differentiated histology and longer survival, low content of uPAR in the poorly differentiated tumors and metastases presumably results from increased elimination of uPAR. (C) 2003 Wiley-Liss, Inc.
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