| 1. |
- Cervenak, L, et al.
(författare)
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Abolished angiogenicity and tumorigenicity of Burkitt lymphoma by interleukin-10
- 2000
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Ingår i: Blood. - 0006-4971. ; 96:7, s. 73-2568
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Tidskriftsartikel (refereegranskat)abstract
- Because of its immunosuppressive properties, interleukin-10 (IL-10) is thought to play an important role in a number of human disease states, including inflammation, autoimmunity, and transplant rejection. In this study, we demonstrate that introduction of human or viral IL-10 genes into Burkitt's lymphoma cells markedly reduced their ability to grow as subcutaneous (sc) tumors in SCID mice. In vivo assays for angiogenesis revealed an inhibition of the angiogenic capacity of the IL-10-transfected lines. Recombinant human IL-10 abolished and viral IL-10 reduced vascular endothelial growth factor (VEGF)-165-induced neovascularization. Furthermore, IL-10 blocked the VEGF- and fibroblast growth factor (FGF)-2-induced proliferation of microvascular endothelial cells in vitro. The current observations suggest a direct role for IL-10 in the prevention of angiogenesis in human lymphoid malignancies.
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| 2. |
- Lehn, Sophie, et al.
(författare)
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Decreased expression of Yes-associated protein is associated with outcome in the luminal A breast cancer subgroup and with an impaired tamoxifen response
- 2014
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Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Yes-associated protein (YAP1) is frequently reported to function as an oncogene in many types of cancer, but in breast cancer results remain controversial. We set out to clarify the role of YAP1 in breast cancer by examining gene and protein expression in subgroups of patient material and by downregulating YAP1 in vitro and studying its role in response to the widely used anti-estrogen tamoxifen. Methods: YAP1 protein intensity was scored as absent, weak, intermediate or strong in two primary breast cancer cohorts (n = 144 and n = 564) and mRNA expression of YAP1 was evaluated in a gene expression dataset (n = 1107). Recurrence-free survival was analysed using the log-rank test and Cox multivariate analysis was used to test for independence. WST-1 assay was employed to measure cell viability and a luciferase ERE (estrogen responsive element) construct was used to study the effect of tamoxifen, following downregulation of YAP1 using siRNAs. Results: In the ER+ (Estrogen Receptor a positive) subgroup of the randomised cohort, YAP1 expression was inversely correlated to histological grade and proliferation (p = 0.001 and p = 0.016, respectively) whereas in the ER-(Estrogen Receptor a negative) subgroup YAP1 expression correlated positively to proliferation (p = 0.005). Notably, low YAP1 mRNA was independently associated with decreased recurrence-free survival in the gene expression dataset, specifically for the luminal A subgroup (p < 0.001) which includes low proliferating tumours of lower grade, usually associated with a good prognosis. This subgroup specificity led us to hypothesize that YAP1 may be important for response to endocrine therapies, such as tamoxifen, extensively used for luminal A breast cancers. In a tamoxifen randomised patient material, absent YAP1 protein expression was associated with impaired tamoxifen response which was significant upon interaction analysis (p = 0.042). YAP1 downregulation resulted in increased progesterone receptor (PgR) expression and a delayed and weaker tamoxifen in support of the clinical data. Conclusions: Decreased YAP1 expression is an independent prognostic factor for recurrence in the less aggressive luminal A breast cancer subgroup, likely due to the decreased tamoxifen sensitivity conferred by YAP1 downregulation.
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| 3. |
- Osada, H, et al.
(författare)
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Association of erythroid transcription factors : complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1
- 1995
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Ingår i: Proceedings of the National Academy of Sciences. - 0027-8424. ; 92:21, s. 9-9585
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Tidskriftsartikel (refereegranskat)abstract
- The RBTN2 LIM-domain protein, originally identified as an oncogenic protein in human T-cell leukemia, is essential for erythropoiesis. A possible role for RBTN2 in transcription during erythropoiesis has been investigated. Direct interaction of the RBTN2 protein was observed in vivo and in vitro with the GATA1 or -2 zinc-finger transcription factors, as well as with the basic helix-loop-helix protein TAL1. By using mammalian two-hybrid analysis, complexes involving RBTN2, TAL1, and GATA1, together with E47, the basic helix-loop-helix heterodimerization partner of TAL1, could be demonstrated. Thus, a molecular link exists between three proteins crucial for erythropoiesis, and the data suggest that variations in amounts of complexes involving RBTN2, TAL1, and GATA1 could be important for erythroid differentiation.
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| 4. |
- Osada, H, et al.
(författare)
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LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1
- 1997
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Ingår i: Leukemia. - 0887-6924. ; 11:Suppl 3, s. 12-307
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Tidskriftsartikel (refereegranskat)abstract
- The LIM-only protein Lmo2, originally identified as an oncogenic protein in human T cell leukemia, is essential for erythropoiesis. A possible role for Lmo2 in transcription during erythropoiesis has been investigated. Direct interaction of Lmo2 was observed in vitro and in vivo with the zinc finger transcription factor GATA-1, as well as with the basic helix-loop-helix (bHLH) transcription factor Tall. By using mammalian two-hybrid analysis, E47/Tall/Lmo2/GATA-1 protein complex could be demonstrated. Thus, a molecular link exists between three proteins crucial for erythropoiesis. This data suggest that variations in amounts of complexes involving Lmo2, Tall, and GATA-1 could be important for erythroid differentiation.
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| 5. |
- Rabbitts, T H, et al.
(författare)
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Chromosomal translocations and leukaemia : a role for LMO2 in T cell acute leukaemia, in transcription and in erythropoiesis
- 1997
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Ingår i: Leukemia. - 0887-6924. ; 11:Suppl 3, s. 2-271
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Tidskriftsartikel (refereegranskat)abstract
- The LMO2 gene associated with T cell acute leukaemia has been used as an example of a gene activated by association with the T cell receptor genes after chromosomal translocations. The gene is shown to encode a LIM protein which is involved in protein interactions and during normal haematopoiesis is necessary for erythroid development. LMO2 has been shown to cause tumours when aberrantly expressed and to be able to heterodimerise with TAL1 to facilitate tumour development.
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| 6. |
- Ahlberg, M., et al.
(författare)
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Time without PSA recurrence after radical prostatectomy as a predictor of prostate cancer death
- 2022
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Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:Suppl. 1, s. S286-S286
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Introduction & Objectives: Although surveillance after radical prostatectomy routinely includes repeated Prostate Specific Antigen (PSA)-testing for many years, biochemical recurrence often occurs without further clinical progression. We therefore hypothesised that follow-up can be shortened for many patients without increasing the risk for prostate cancer death. We investigated the long-term probabilities of PSA recurrence, metastases and prostate cancer death in patients without biochemical recurrence 5 and 10 years after radical prostatectomy.Materials & Methods: Between 1989 and 1998, 14 urological centres in Scandinavia randomized patients to the Scandinavian Prostate Cancer Group study number 4 (SPCG-4) trial. Data was collected prospectively. All 306 patients from the SPCG-4 trial who underwent radical prostatectomy within 1 year from inclusion were eligible in our cohort. 4 patients were excluded due to surgery-related death (n=1) or salvage radiotherapy or hormonal treatment within 6 weeks from surgery (n=3). We stratified by Gleason score (≤3+4=7 or ≥4+3=7), pathological tumour stage (pT2 or ≥pT3), and negative or positive surgical margins. We analysed the cumulative incidences and absolute differences in metastatic disease and prostate cancer death.Results: We analysed 302 patients with complete follow-up during a median of 18 years. Median preoperative PSA was 9.8 ng/ml and median age at inclusion was 65 years. For patients without biochemical recurrence 5 years after radical prostatectomy the 20-year probability of biochemical recurrence was 25% among men with Gleason score ≤3+4=7 and 57% among men with Gleason score ≥4+3=7; the probabilities for metastases were 0.8% and 17%; and for prostate cancer death 0.8% and 12% respectively. The long-term probabilities were higher for pT≥3 vs. pT2 and for positive vs. negative surgical margins.Conclusions: Following radical prostatectomy, patients with Gleason score ≤3+4=7 without biochemical recurrence 5 years after radical prostatectomy had low risk of metastases and prostate cancer death independent of pT-stage and surgical margins. The risk of clinical progression decreased drastically the first 3 years after radical prostatectomy and after 10 years without biochemical recurrence, no patient was diagnosed with metastases or died from prostate cancer. Our study indicates that men with favourable histopathology without biochemical recurrence 5 years after radical prostatectomy can stop follow-up earlier than 10 years after radical prostatectomy while men with adverse pathology should continue with at least 10 years follow-up
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| 7. |
- Axelson, H, et al.
(författare)
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A new variant 15; 16 translocation in mouse plasmacytoma leads to the juxtaposition of c-myc and immunoglobulin lambda
- 1991
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Ingår i: Oncogene. - 0950-9232. ; 6:12, s. 70-2263
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Tidskriftsartikel (refereegranskat)abstract
- Mouse plasmacytomas (MPCs) induced by pristane oil, or by a combination of pristane oil and Abelson virus, carry one of two chromosomal translocations. The typical 12; 15 translocation leads to the juxtaposition of c-myc and immunoglobulin heavy-chain sequences, whereas the 6; 15 translocation links the kappa light-chain locus with the pvt-1 (plasmacytoma variant translocation) locus, located at least 75kb 3' of c-myc [Cory, S., Graham, M., Webb, E., Corcoran, L. & Adams, J. (1985). EMBO J., 4, 675-681]. Unlike the human Burkitt's lymphoma-associated translocation, the lambda/myc juxtaposed variant translocation has not been found previously in MPCs. Using unconventional MPC induction systems in which the tumor precursor cell was induced to proliferate in a secondary host, we have recently identified a 15; 16 translocation in six of the derived MPCs [Wiener, F., Silva, S., Sugiyama, H., Babonits, M. & Klein, G. (1990). Genes Chromosomes Cancer, 2, 36-43]. Chromosome 16 harbors the lambda light-chain gene. To explore whether the 15; 16 translocation represents the lambda/myc juxtaposition, we have mapped the breakpoints on chromosomes 15 and 16 by pulsed-field gel electrophoresis (PFGE). The pvt-1 region was mapped to approximately 220 kb 3' of c-myc. The breakpoint on chromosome 15 in ABPC-Ch-163-10, one of the six 15; 16 translocation-carrying MPCs, was situated approximately 80 kb 3' of c-myc and 140 kb 5' of pvt-1b, the major breakpoint cluster region of the previously analysed 6; 15 variant MPCs. The breakpoint on chromosome 16 was found to cut between the V1 and C3 regions of the lambda locus. Co-migration experiments showed that the C3 and the myc gene were juxtaposed head to tail on the 15; 16 translocation chromosome. On the reciprocal product V1 was juxtaposed to pvt-1.
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| 8. |
- Lange, Jane M., et al.
(författare)
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Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts
- 2020
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Ingår i: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 126:3, s. 583-592
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Tidskriftsartikel (refereegranskat)abstract
- Background Active surveillance (AS) is an accepted means of managing low-risk prostate cancer. Because of the rarity of downstream events, data from existing AS cohorts cannot yet address how differences in surveillance intensity affect metastasis and mortality. This study projected the comparative benefits of different AS schedules in men diagnosed with prostate cancer who had Gleason score (GS) <= 6 disease and risk profiles similar to those in North American AS cohorts. Methods Times of GS upgrading were simulated based on AS data from the University of Toronto, Johns Hopkins University, the University of California at San Francisco, and the Canary Pass Active Surveillance Cohort. Times to metastasis and prostate cancer death, informed by models from the Scandinavian Prostate Cancer Group 4 trial, were projected under biopsy surveillance schedules ranging from watchful waiting to annual biopsies. Outcomes included the risk of metastasis, the risk of death, remaining life-years (LYs), and quality-adjusted LYs. Results Compared with watchful waiting, AS biopsies reduced the risk of prostate cancer metastasis and prostate cancer death at 20 years by 1.4% to 3.3% and 1.0% to 2.4%, respectively; and 5-year biopsies reduced the risk of metastasis and prostate cancer death by 1.0% to 2.4% and 0.6% to 1.6%, respectively. There was little difference between annual and 5-year biopsy schedules in terms of LYs (range of differences, 0.04-0.16 LYs) and quality-adjusted LYs (range of differences, -0.02 to 0.09 quality-adjusted LYs). Conclusions Among men diagnosed with GS <= 6 prostate cancer, obtaining a biopsy every 3 or 4 years appears to be an acceptable alternative to more frequent biopsies. Reducing surveillance intensity for those who have a low risk of progression reduces the number of biopsies while preserving the benefit of more frequent schedules.
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| 9. |
- Lazar, J., et al.
(författare)
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Human-computer interaction and international public policymaking : A framework for understanding and taking future actions
- 2015
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Ingår i: Foundations and Trends in Human-Computer Interaction. - : Now Publishers Inc.. - 1551-3955 .- 1551-3963. ; 9:2, s. 69-149
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Tidskriftsartikel (refereegranskat)abstract
- This monograph lays out a discussion framework for understanding the role of human-computer interaction (HCI) in public policymaking. We take an international view, discussing potential areas for research and application, and their potential for impact. Little has been written about the intersection of HCI and public policy; existing reports typically focus on one specific policy issue or incident. To date, there has been no overarching view of the areas of existing impact and potential impact. We have begun that analysis and argue here that such a global view is needed. Our aims are to provide a solid foundation for discussion, cooperation and collaborative interaction, and to outline future programs of activity. The five sections of this report provide relevant background along with a preliminary version of what we expect to be an evolving framework. Sections 1 and 2 provides an introduction to HCI and public policy. Section 3 discusses how HCI already informs public policy, with representative examples. Section 4 discusses how public policy influences HCI and provides representative public policy areas relevant to HCI, where HCI could have even more impact in the future: (i) laws, regulations, and guidelines for HCI research, (ii) HCI research assessments, (iii) research funding, (iv) laws for interface design - accessibility and language, (v) data privacy laws and regulations, (vi) intellectual property, and (vii) laws and regulations in specific sectors. There is a striking difference between where the HCI community has had impact (Section 3) and the many areas of potential involvement (Section 4). Section 5 a framework for action by the HCI community in public policy internationally. This monograph summarizes the observations and recommendations from a daylong workshop at the CHI 2013 conference in Paris, France. The workshop invited the community's perspectives regarding the intersection of governmental policies, international and domestic standards, recent HCI research discoveries, and emergent considerations and challenges. It also incorporates contributions made after the workshop by workshop participants and by individuals who were unable to participate in the workshop but whose work and interests were highly related and relevant.
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| 10. |
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