| 1. |
- Cervenak, L, et al.
(författare)
-
Abolished angiogenicity and tumorigenicity of Burkitt lymphoma by interleukin-10
- 2000
-
Ingår i: Blood. - 0006-4971. ; 96:7, s. 73-2568
-
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.
|
|
| 2. |
- Lehn, Sophie, et al.
(författare)
-
Decreased expression of Yes-associated protein is associated with outcome in the luminal A breast cancer subgroup and with an impaired tamoxifen response
- 2014
-
Ingår i: Bmc Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14
-
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.
|
|
| 3. |
- Osada, H, et al.
(författare)
-
Association of erythroid transcription factors : complexes involving the LIM protein RBTN2 and the zinc-finger protein GATA1
- 1995
-
Ingår i: Proceedings of the National Academy of Sciences. - 0027-8424. ; 92:21, s. 9-9585
-
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.
|
|
| 4. |
- Osada, H, et al.
(författare)
-
LIM-only protein Lmo2 forms a protein complex with erythroid transcription factor GATA-1
- 1997
-
Ingår i: Leukemia. - 0887-6924. ; 11:Suppl 3, s. 12-307
-
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.
|
|
| 5. |
- Rabbitts, T H, et al.
(författare)
-
Chromosomal translocations and leukaemia : a role for LMO2 in T cell acute leukaemia, in transcription and in erythropoiesis
- 1997
-
Ingår i: Leukemia. - 0887-6924. ; 11:Suppl 3, s. 2-271
-
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.
|
|
| 6. |
- Ahlberg, M., et al.
(författare)
-
Time without PSA recurrence after radical prostatectomy as a predictor of prostate cancer death
- 2022
-
Ingår i: European Urology. - : Elsevier. - 0302-2838 .- 1873-7560. ; 81:Suppl. 1, s. S286-S286
-
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
|
|
| 7. |
- Axelson, H, et al.
(författare)
-
A new variant 15; 16 translocation in mouse plasmacytoma leads to the juxtaposition of c-myc and immunoglobulin lambda
- 1991
-
Ingår i: Oncogene. - 0950-9232. ; 6:12, s. 70-2263
-
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.
|
|
| 8. |
- Lange, Jane M., et al.
(författare)
-
Prostate cancer mortality and metastasis under different biopsy frequencies in North American active surveillance cohorts
- 2020
-
Ingår i: Cancer. - : WILEY. - 0008-543X .- 1097-0142. ; 126:3, s. 583-592
-
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.
|
|
| 9. |
- Lazar, J., et al.
(författare)
-
Human-computer interaction and international public policymaking : A framework for understanding and taking future actions
- 2015
-
Ingår i: Foundations and Trends in Human-Computer Interaction. - : Now Publishers Inc.. - 1551-3955 .- 1551-3963. ; 9:2, s. 69-149
-
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.
|
|
| 10. |
|
|
| 11. |
- Sánchez-García, I, et al.
(författare)
-
Functional diversity of LIM proteins : amino-terminal activation domains in the oncogenic proteins RBTN1 and RBTN2
- 1995
-
Ingår i: Oncogene. - 0950-9232. ; 10:7, s. 6-1301
-
Tidskriftsartikel (refereegranskat)abstract
- The RBTN1 and RBTN2 genes are activated by distinct translocations involving chromosome 11 in some T cell acute leukaemias. The RBTN proteins belong to the LIM family which comprises proteins with one, two or three cysteine-rich LIM domains, sometimes together with homeodomains or protein kinase domains. The RBTN1 and RBTN2 proteins comprise only tandem LIM domains. We report that RBTN1 and RBTN2 proteins are capable of supporting transcriptional transactivation of specific reporter genes in transfection assays. The results, using intact proteins or fusions with the homeodomain of the heterologous protein Isl-1, show that this transcriptional activation ability resides in the NH2-terminal parts of both proteins. The use of yeast assays with RBTN2 shows that RBTN2 forms homodimers and that the NH2-terminal 27 amino acids are sufficient to facilitate transcriptional transactivation. These data expand the functional diversity of the LIM-domain protein family and they augment the previously defined relationship between chromosomal translocations and transcriptional activation.
|
|
| 12. |
- Simpkin, Andrew J., et al.
(författare)
-
Prostate-specific antigen patterns in US and European populations : comparison of six diverse cohorts
- 2016
-
Ingår i: BJU International. - : Wiley. - 1464-4096 .- 1464-410X. ; 118:6, s. 911-918
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine whether there are differences in prostate-specific antigen (PSA) levels at diagnosis or changes in PSA levels between US and European populations of men with and without prostate cancer (PCa).SUBJECTS AND METHODS: We analysed repeated measures of PSA from six clinically and geographically diverse cohorts of men: two cohorts with PSA-detected PCa, two cohorts with clinically detected PCa and two cohorts without PCa. Using multilevel models, average PSA at diagnosis and PSA change over time were compared among study populations.RESULTS: The annual percentage PSA change of 4-5% was similar between men without cancer and men with PSA-detected cancer. PSA at diagnosis was 1.7 ng/mL lower in a US cohort of men with PSA-detected PCa (95% confidence interval 1.3-2.0 ng/mL), compared with a UK cohort of men with PSA-detected PCa, but there was no evidence of a different rate of PSA change between these populations.CONCLUSION: We found that PSA changes over time are similar in UK and US men diagnosed through PSA testing and even in men without PCa. Further development of PSA models to monitor men on active surveillance should be undertaken in order to take advantage of these similarities. We found no evidence that guidelines for using PSA to monitor men cannot be passed between US and European studies.
|
|
| 13. |
- Visintin, M, et al.
(författare)
-
Selection of antibodies for intracellular function using a two-hybrid in vivo system
- 1999
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 96:21, s. 8-11723
-
Tidskriftsartikel (refereegranskat)abstract
- Expression of antibodies inside cells has been used successfully to ablate protein function. This finding suggests that the technology should have an impact on disease treatment and in functional genomics where proteins of unknown function are predicted from genomic sequences. A major hindrance is the paucity of antibodies that function in eukaryotic cells, presumably because the antibodies fold incorrectly in the cytoplasm. To overcome this problem, we have developed an in vivo assay for functional intracellular antibodies using a two-hybrid approach. In this assay, antibody, as single-chain Fv (scFv) linked to a transcriptional transactivation domain, can interact with a target antigen, linked to a LexA-DNA binding domain, and thereby activate a reporter gene. We find that several characterized antibodies can bind their target antigen in eukaryotic cells in this two-hybrid format, and we have been able to isolate intracellular binders from among sets of scFv that can bind antigen in vitro. Furthermore, we show a model selection in which a single scFv was isolated from a mixture of half a million clones, indicating that this is a robust procedure that should facilitate capture of antibody specificities from complex mixtures. The approach can provide the basis for de novo selection of intracellular scFv from libraries, such as those made from spleen RNA after immunization with antigen, for intracellular analysis of protein function based only on genomic or cDNA sequences.
|
|
| 14. |
- Wang, Y, et al.
(författare)
-
Functional homology between N-myc and c-myc in murine plasmacytomagenesis : plasmacytoma development in N-myc transgenic mice
- 1992
-
Ingår i: Oncogene. - 0950-9232. ; 7:6, s. 7-1241
-
Tidskriftsartikel (refereegranskat)abstract
- Mouse plasmacytomas induced by pristane oil alone, or in combination with Abelson murine leukemia virus (A-MuLV), regularly carry one of three alternative chromosomal translocations that juxtapose c-myc to immunoglobulin heavy- or light-chain loci. E mu-c-myc transgenic mice develop translocation-free plasmacytomas after induction by pristane oil and/or A-MuLV [Sugiyama, H., Silva, S., Wang, Y., Weber, G., Babonits, M., Rosen, A., Wiener, F. & Klein, G. (1990). Int. J. Cancer, 46, 845-852]. In order to test whether another member of the myc family, N-myc, could play a similar role as c-myc, we treated E mu-N-myc transgenic mice with pristane and helper-free A-MuLV. Of 20 mice that received a single pristane injection followed by A-MuLV, 17 developed plasmacytomas with a mean latency period of 54 +/- 20 days. In a corresponding group that only received a single pristane injection, five out of six transgenic mice developed plasmacytomas with a mean latency period of 142 +/- 32 days. However, after three monthly injections of pristane, all 15 transgenic mice developed plasmacytomas with a mean latency period of 128 +/- 20 days. All plasmacytomas expressed the N-myc transgene, while none of them expressed either c-myc or endogenous N-myc. None of the tumors carried the usual plasmacytoma-associated translocations.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
- Ahmadi, Ahmad, 1964-, et al.
(författare)
-
GSTM1 and mEPHX polymorphisms in Parkinson's disease and age of onset
- 2000
-
Ingår i: Biochemical and Biophysical Research Communications - BBRC. - : Elsevier BV. - 0006-291X .- 1090-2104. ; 269:3, s. 676-680
-
Tidskriftsartikel (refereegranskat)abstract
- Both environmental and genetic factors are involved in the development of PD and biotransformation of exogenous and endogenous compounds and may play a role in inter-individual susceptibility. Therefore, we investigated the presence of null genotypes of GSTM1, GSTT1, and two polymorphisms of mEPHX in subjects with Parkinson's disease and in a reference population. The study included 35 male PD patients and a male control group including 283 subjects. Homozygosity of the histidine (H) 113 isoform of mEPHX was significantly increased in PD patients (odds ratio = 3.8 CI 95% 1.2–11.8) and analysis of allele frequencies displayed an increased frequency of the H-allele among PD patients (odds ratio = 1.9 CI 95% 1.1–3.3). However, a significantly elevated median age for the onset of PD was found among GSTM1 gene carriers (median age = 68 years) compared to PD patients being GSTM1 null genotypes (median age = 57 years). Our observations suggest that (H) 113 isoform of mEPHX, which has been suggested as a low activity isoform, is overrepresented in PD patients and that inherited carriers of the GSTM1 gene postpone the onset of PD. These detoxification pathways may represent important protective mechanisms against reactive intermediates modifying the susceptibility and onset of PD.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Axelson, H, et al.
(författare)
-
Juxtaposition of N-myc and Ig kappa through a reciprocal t(6;12) translocation in a mouse plasmacytoma
- 1994
-
Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 11:2, s. 85-90
-
Tidskriftsartikel (refereegranskat)abstract
- Nearly all mouse plasmacytomas (MPCs) carry an Ig/myc translocation. Any one of the three Ig loci may participate, while the myc contribution has been limited to c-myc, excluding other members of the myc gene family. The same is true for the other two known Ig/myc translocation-carrying tumors, Burkitt's lymphoma and rat immunocytoma. It is believed that the Ig/myc juxtaposition plays a decisive, rate limiting role in the genesis of the three tumors, acting through the constitutive activation of myc that makes it refractory to normal regulation. Here we describe the molecular analysis of a unique t(6;12)(CI;B) translocation that we previously identified in an exceptional MPC that expressed N-myc but not c-myc. We now show that the translocation led to the juxtaposition of N-myc and Ig kappa. This is the first case of an Ig/myc-carrying tumor that involves N-myc rather than c-myc. These findings suggest that the translocation may already have occurred at the pro- or pre-B cell stage at which N-myc is open for transcription. According to this interpretation, constitutive activation of N-myc would suppress the expression of c-myc, but would not interfere with the differentiation of the pro-B cell into a fully mature plasma cell. Its tumorigenic influence would become manifest only at the time when the cell would normally be programmed to leave the cycling compartment, in connection with its terminal differentiation.
|
|
| 21. |
- Axelson, H, et al.
(författare)
-
The amino-terminal phosphorylation sites of C-MYC are frequently mutated in Burkitt's lymphoma lines but not in mouse plasmacytomas and rat immunocytomas
- 1995
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 31A:12, s. 104-2099
-
Tidskriftsartikel (refereegranskat)abstract
- We sequenced the region encoding the amino-terminal phosphorylation sites of C-MYC in the Ig/MYC translocation-carrying Burkitt lymphomas (BL), mouse plasmacytomas (MPC) and rat immunocytomas (RIC). Mutations affecting the Thr-58 codon or the immediate flanking region were found in seven of the 10 in vitro propagated BL lines. No mutations were found in any of the eight BL biopsies analysed. Germ-line sequences were also found in six in vivo and five in vitro passaged MPCs and in four in vivo transplanted RICs. These findings indicate that mutations in this region do not represent a general phenomena in Ig/MYC translocation-carrying tumours, but may confer growth advantage on BL cells under continuous in vitro propagation.
|
|
| 22. |
- Axelson, H, et al.
(författare)
-
Three exceptional IgH/myc-translocation-carrying rat immunocytomas have breakpoints 50 to 80 kb 5' of c-myc
- 1994
-
Ingår i: International Journal of Cancer. - 0020-7136. ; 56:3, s. 21-418
-
Tidskriftsartikel (refereegranskat)abstract
- The spontaneously arising immunocytoma of the Louvain rat (RIC) carries a consistent chromosomal translocation between chromosomes 6 and 7. This translocation juxtaposes immunoglobulin heavy chain and c-myc sequences. In an earlier study on 14 RIC tumors, we found that the translocation breakpoint is located within 1.5 kb immediately upstream of c-myc in 10 of the tumors. Here we describe 3 exceptional tumors that had no rearrangement within 20 kb 5' of c-myc. Using pulsed-field gel electrophoresis we show that the translocation breakpoints in these tumors are located 50-80 kb 5' of c-myc and that c-myc rearranges to the 3' end of the IgH cluster.
|
|
| 23. |
|
|
| 24. |
- Axelson, Olav, 1937-, et al.
(författare)
-
Regulatory toxicology and pharmacology.
- 2003
-
Ingår i: International journal of occupational and environmental health. - 1077-3525 .- 2049-3967. ; 9, s. 386-389
-
Tidskriftsartikel (refereegranskat)
|
|
| 25. |
- Bergengren, Oskar, et al.
(författare)
-
Determinants for choosing and adhering to active surveillance for localised prostate cancer: A nationwide population-based study
- 2019
-
Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 9:12
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Knowledge about factors influencing choice of and adherence to active surveillance (AS) for prostate cancer (PC) is scarce. We aim to identify which factors most affected choosing and adhering to AS and to quantify their relative importance. Design, setting and participants In 2015, we sent a questionnaire to all Swedish men aged ≤70 years registered in the National Prostate Cancer Register of Sweden who were diagnosed in 2008 with low-risk PC and had undergone prostatectomy, radiotherapy or started on AS. Outcome measurements and statistical analysis Logistic regression was used to calculate ORs with 95% CIs for factors potentially affecting choice and adherence to AS. Results 1288 out of 1720 men (75%) responded, 451 (35%) chose AS and 837 (65%) underwent curative treatment. Of those starting on AS, 238 (53%) diverted to treatment within 7years. Most men (83%) choose AS because ‘My doctor recommended AS’. Factors associated with choosing AS over treatment were older age (OR 1.81, 95%CI 1.29 to 2.54), a Charlson Comorbidity Index >2 (OR 1.50, 95%CI 1.06 to 2.13), being unaccompanied when notified of the cancer diagnosis (OR 1.45, 95%CI 1.11 to 1.89). Men with a higher prostate-specific antigen (PSA) at the time of diagnosis were less likely to adhere to AS (OR 0.26, 95%CI 0.10 to 0.63). The reason for having treatment after initial AS was ‘the PSA level was rising’ in 55% and biopsy findings in 36%. Conclusions A doctor’s recommendation strongly affects which treatment is chosen for men with low-risk PC. Rising PSA values were the main factor for initiating treatment for men on AS. These findings need be considered by healthcare providers who wish to increase the uptake of and adherence to AS.
|
|
| 26. |
- Bergengren, Oskar, et al.
(författare)
-
Satisfaction with Care Among Men with Localised Prostate Cancer: A Nationwide Population-based Study
- 2018
-
Ingår i: European Urology Oncology. - : Elsevier BV. - 2588-9311. ; 1:1, s. 37-45
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Information about how men with prostate cancer (PC) experience their medical care and factors associated with their overall satisfaction with care (OSC) is limited. Objective: To investigate OSC and factors associated with OSC among men with low-risk PC. Design, setting, and participants: Men registered in the National Prostate Cancer Register of Sweden as diagnosed in 2008 with low-risk PC at the age of ≤70 yr who had undergone radical prostatectomy (RP), radiotherapy (RT), or started on active surveillance (AS) were invited in 2015 to participate in this nationwide population-based survey (n = 1720). Outcome measurements and statistical analysis: OSC data were analysed using ordinal logistic regression. Odds ratios (ORs) were calculated for comparisons between the highest and lowest possible response categories. Results and limitations: A total of 1288 men (74.9%) responded. High OSC was reported by 958 (74.4%). Factors associated with high OSC were high participation in decision-making (OR 4.18, 95% confidence interval [CI] 2.61–6.69), receiving more information (OR 11.1, 95% CI 7.97–15.6), high-quality information (OR 7.85, 95% CI 5.46–11.3), access to a nurse navigator (OR 1.80, 95% CI 1.44–2.26), and better functional outcomes (defined as 25 points higher on the EPIC-26 questionnaire; OR 1.34, 95% CI 1.21–1.48). OSC was not affected by whether a doctor or specialist nurse conducted follow-up (OR 0.84, 95% CI 0.66–1.07). These findings were similar across treatment groups. Men who had undergone RP or RT reported high OSC more often than men on AS (78.2% vs 84.0% vs 72.6%), high participation in decision-making (70.5% vs 64.5% vs 49.2%), and having received more information (40.5% vs 45.8% vs 28.6%), and were less likely to believe they would die from PC (3.8% vs 3.9% vs 8.0%). Limitations include the nonrandomised retrospective design and potential recall bias. Conclusions: Information and participation in decision-making, as well as access to a nurse navigator, are key factors for OSC, regardless of treatment. Men on AS need more information about their treatment and need to participate more in decision-making. OSC was as high among men who had nurse-led follow-up as among men who had doctor-led follow-up. Patient summary: Information about how men with low-risk prostate cancer experience their medical care is limited. In this nationwide population-based study we found that information and participation in decision-making as well as access to a nurse navigator are key factors for satisfaction regardless of treatment. Men who are being closely watched for prostate cancer without immediate curative treatment need more information than they now receive and need to participate more in decision-making than they currently do. Information and participation in decision-making are key factors for satisfaction with care among men with localised prostate cancer. Men under active surveillance need more information about their treatment and need to participate more in decision-making. © 2018 European Association of Urology
|
|
| 27. |
- Bergengren, Oskar, et al.
(författare)
-
Short term outcomes after robot assisted and open cystectomy- A nation-wide population-based study
- 2023
-
Ingår i: Ejso. - : Elsevier BV. - 0748-7983 .- 1532-2157. ; 49:4, s. 868-874
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: We aimed to compare short term outcomes after robot assisted radical cystectomy (RARC) and open radical cystectomy (ORC) for urinary bladder cancer in a large population.Materials and methods: We included all patients without distant metastases who underwent either RARC or ORC with ileal conduit between 2011 and 2019 registered in the Bladder cancer data Base Sweden (BladderBaSe) 2.0. Primary outcome was unplanned readmissions within 90 days, and secondary out-comes within 90 days of surgery were reoperations, Clavien 3-5 complications, total days alive and out of hospital, and mortality. The analysis was carried out using multivariate regression models.Results: Out of 2905 patients, 832 were operated with RARC and 2073 with ORC. Robotic procedures were to a larger extent performed during later years, at high volume centers (47% vs 17%), more often for organ-confined disease (82% vs. 72%) and more frequently in patients with high socioeconomic status (26% vs. 21%). Patients operated with RARC were more commonly readmitted (29% vs. 25%). In multi -variable analysis RARC was associated with decreased risk of Clavien 3-5 complications (OR 0.58, 95% CI 0.47-0.72), reoperations (OR 0.53, 95% CI 0.39-0.71) and had more days alive and out of hospital (mean difference 3.7 days, 95% CI 2.4-5.0).Conclusion: This study illustrates the "real-world" effects of a gradual and nation-wide introduction of RARC. Patients operated with RARC had fewer major complications and reoperations but were more frequently readmitted compared to ORC. The observed differences were largely due to more wound related complications among patients treated with ORC.(c) 2023 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
|
|
| 28. |
- Bill-Axelson, Anna, et al.
(författare)
-
Radical Prostatectomy or Watchful Waiting in Prostate Cancer-29-Year Follow-up
- 2018
-
Ingår i: New England Journal of Medicine. - : Massachussetts Medical Society. - 0028-4793 .- 1533-4406. ; 379:24, s. 2319-2329
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Radical prostatectomy reduces mortality among men with clinically detected localized prostate cancer, but evidence from randomized trials with long-term followup is sparse. METHODS We randomly assigned 695 men with localized prostate cancer to watchful waiting or radical prostatectomy from October 1989 through February 1999 and collected follow-up data through 2017. Cumulative incidence and relative risks with 95% confidence intervals for death from any cause, death from prostate cancer, and metastasis were estimated in intention-to-treat and per-protocol analyses, and numbers of years of life gained were estimated. We evaluated the prognostic value of histopathological measures with a Cox proportional-hazards model. RESULTS By December 31, 2017, a total of 261 of the 347 men in the radical-prostatectomy group and 292 of the 348 men in the watchful-waiting group had died; 71 deaths in the radical-prostatectomy group and 110 in the watchful-waiting group were due to prostate cancer (relative risk, 0.55; 95% confidence interval [CI], 0.41 to 0.74; P<0.001; absolute difference in risk, 11.7 percentage points; 95% CI, 5.2 to 18.2). The number needed to treat to avert one death from any cause was 8.4. At 23 years, a mean of 2.9 extra years of life were gained with radical prostatectomy. Among the men who underwent radical prostatectomy, extracapsular extension was associated with a risk of death from prostate cancer that was 5 times as high as that among men without extracapsular extension, and a Gleason score higher than 7 was associated with a risk that was 10 times as high as that with a score of 6 or lower (scores range from 2 to 10, with higher scores indicating more aggressive cancer). CONCLUSIONS Men with clinically detected, localized prostate cancer and a long life expectancy benefited from radical prostatectomy, with a mean of 2.9 years of life gained. A high Gleason score and the presence of extracapsular extension in the radical prostatectomy specimens were highly predictive of death from prostate cancer.
|
|
| 29. |
- Bill-Axelson, Anna, et al.
(författare)
-
Radical prostatectomy versus watchful waiting in localized prostate cancer : the Scandinavian prostate cancer group-4 randomized trial
- 2008
-
Ingår i: Journal of the National Cancer Institute. - : Oxford University Press. - 0027-8874 .- 1460-2105. ; 100:16, s. 1144-1154
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery.
|
|
| 30. |
- Braekeveldt, N., et al.
(författare)
-
Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma
- 2018
-
Ingår i: Cancer Research. - 0008-5472. ; 78:20, s. 5958-5969
-
Tidskriftsartikel (refereegranskat)abstract
- Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain under-explored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we captured spatial intratumor heterogeneity using ten PDXs from a single high-risk patient tumor. We observed diverse growth rates, transcriptional, proteomic, and phosphoproteomic profiles. PDX-derived transcriptional profiles were associated with diverse clinical characteristics in patients with high-risk neuroblastoma. These data suggest that high-risk neuroblastoma contains elements of both temporal stability and spatial intratumor heterogeneity, the latter of which complicates clinical translation of personalized PDX-Avatar studies into preclinical cancer research. Significance: These findings underpin the complexity of PDX modeling as a means to advance translational applications against neuroblastoma. (C) 2018 AACR.
|
|
| 31. |
|
|
| 32. |
|
|
| 33. |
- Glimelius, Bengt, et al.
(författare)
-
U-CAN : a prospective longitudinal collection of biomaterials and clinical information from adult cancer patients in Sweden.
- 2018
-
Ingår i: Acta Oncologica. - : Taylor & Francis. - 0284-186X .- 1651-226X. ; 57:2, s. 187-194
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Progress in cancer biomarker discovery is dependent on access to high-quality biological materials and high-resolution clinical data from the same cases. To overcome current limitations, a systematic prospective longitudinal sampling of multidisciplinary clinical data, blood and tissue from cancer patients was therefore initiated in 2010 by Uppsala and Umeå Universities and involving their corresponding University Hospitals, which are referral centers for one third of the Swedish population.Material and Methods: Patients with cancer of selected types who are treated at one of the participating hospitals are eligible for inclusion. The healthcare-integrated sampling scheme encompasses clinical data, questionnaires, blood, fresh frozen and formalin-fixed paraffin-embedded tissue specimens, diagnostic slides and radiology bioimaging data.Results: In this ongoing effort, 12,265 patients with brain tumors, breast cancers, colorectal cancers, gynecological cancers, hematological malignancies, lung cancers, neuroendocrine tumors or prostate cancers have been included until the end of 2016. From the 6914 patients included during the first five years, 98% were sampled for blood at diagnosis, 83% had paraffin-embedded and 58% had fresh frozen tissues collected. For Uppsala County, 55% of all cancer patients were included in the cohort.Conclusions: Close collaboration between participating hospitals and universities enabled prospective, longitudinal biobanking of blood and tissues and collection of multidisciplinary clinical data from cancer patients in the U-CAN cohort. Here, we summarize the first five years of operations, present U-CAN as a highly valuable cohort that will contribute to enhanced cancer research and describe the procedures to access samples and data.
|
|
| 34. |
|
|
| 35. |
- Hendry, Alexandra, et al.
(författare)
-
Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits
- 2020
-
Ingår i: Journal of autism and developmental disorders. - : Springer Nature. - 0162-3257 .- 1573-3432. ; 50:11, s. 4085-4105
-
Tidskriftsartikel (refereegranskat)abstract
- Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals’ mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7–9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.
|
|
| 36. |
- Henriksson, M, et al.
(författare)
-
Nuclear colocalization of c-myc protein and hsp70 in cells transfected with human wild-type and mutant c-myc genes
- 1992
-
Ingår i: Experimental Cell Research. - 0014-4827. ; 203:2, s. 94-383
-
Tidskriftsartikel (refereegranskat)abstract
- Using immunofluorescence and electron microscopy we have studied the localization of wild-type and mutant c-myc proteins transiently expressed in CV-1 cells. In agreement with our previous observations, wild-type c-myc protein accumulated in large amorphous globules in the nucleus. All mutant proteins tested accumulated in the nucleus as well, but gave rise to morphologically different inclusion bodies. Many small globules appeared in cells transfected with D145-262 (deletion of amino acids 145-262), while cells transfected with D371-412 or D414-433 generated structures looking like a fine network or like beads on a string. In addition, a particulate cytoplasmic staining appeared in some cells transfected with the wild-type gene and in cells transfected with mutants D145-262 or D414-433. Since the c-myc protein has been reported to stimulate expression of exogenous hsp70 protein, we also examined the intracellular distribution of hsp70 in the transfected cells. Double immunofluorescence microscopy revealed that hsp70 codistributed with the c-myc protein in distinct globules in the nucleus of many but not all myc-positive cells. However, the levels of hsp70 transcripts were not significantly raised compared to nontransfected and vector-transfected cells. Likewise, the levels of hsp70 protein did not vary significantly. These findings indicate that overexpression of c-myc stimulates translocation of preexisting hsp70 from the cytoplasm into the nucleus, rather than influencing hsp70 expression. Conceivably, this may represent one of several mechanisms whereby the cell deals with excessive amounts of c-myc protein.
|
|
| 37. |
- Heroux, Martin E., et al.
(författare)
-
How we perceive the width of grasped objects: Insights into the central processes that govern proprioceptive judgements
- 2024
-
Ingår i: Journal of Physiology. - : WILEY. - 0022-3751 .- 1469-7793.
-
Tidskriftsartikel (refereegranskat)abstract
- Low-level proprioceptive judgements involve a single frame of reference, whereas high-level proprioceptive judgements are made across different frames of reference. The present study systematically compared low-level (grasp -> grasp) and high-level (vision -> grasp, grasp -> vision) proprioceptive tasks, and quantified the consistency of grasp -> vision and possible reciprocal nature of related high-level proprioceptive tasks. Experiment 1 (n = 30) compared performance across vision -> grasp, a grasp -> vision and a grasp -> grasp tasks. Experiment 2 (n = 30) compared performance on the grasp -> vision task between hands and over time. Participants were accurate (mean absolute error 0.27 cm [0.20 to 0.34]; mean [95% CI]) and precise (R-2 = 0.95 [0.93 to 0.96]) for grasp -> grasp judgements, with a strong correlation between outcomes (r = -0.85 [-0.93 to -0.70]). Accuracy and precision decreased in the two high-level tasks (R-2 = 0.86 and 0.89; mean absolute error = 1.34 and 1.41 cm), with most participants overestimating perceived width for the vision -> grasp task and underestimating it for grasp -> vision task. There was minimal correlation between accuracy and precision for these two tasks. Converging evidence indicated performance was largely reciprocal (inverse) between the vision -> grasp and grasp -> vision tasks. Performance on the grasp -> vision task was consistent between dominant and non-dominant hands, and across repeated sessions a day or week apart. Overall, there are fundamental differences between low- and high-level proprioceptive judgements that reflect fundamental differences in the cortical processes that underpin these perceptions. Moreover, the central transformations that govern high-level proprioceptive judgements of grasp are personalised, stable and reciprocal for reciprocal tasks.
|
|
| 38. |
- Imreh, S, et al.
(författare)
-
Hypersomy of chromosome 15 with retrovirally rearranged c-myc, loss of germline c-myc and IgK/c-myc juxtaposition in a macrophage-monocytic tumour line
- 1994
-
Ingår i: European Journal of Cancer. - 0959-8049. ; 30A:7, s. 994-1002
-
Tidskriftsartikel (refereegranskat)abstract
- From a lymphoid tumour induced by 7,12-dimethylbenz-[a]-anthracene (DMBA) + methyl-N-nitrose-N-urea (MNU) in an [AKR Rb(6.15) x CBAT6T6]F1 mouse, a macrophage- monocyte line (KT-10) was isolated. Following ethyl methanesulfonate (EMS) treatment, a bromodeoxyuridine (BUdR) resistant subline was selected. Serial propagation of this line in vitro in the presence of BUdR (28 months) with periodic cytogenetic and molecular examinations, has led to the definition of four successive stages. During stage I, the cells were trisomic for chromosome 15. They contained Rb(6.15) and Rb(del6.15) of AKR and T(14;15) of CBA origin. Southern blotting showed the presence of both germline (G) and rearranged (R) c-myc. At stage II, Rb(del6.15) has duplicated. Both Rb(6.15) and T(14;15) persisted together with G-myc and R-myc. In stage III, the CBA-derived T(14;15) was lost, in parallel with G-myc. At this stage, a Dic.In(6.15) was detected. One of its arms was cytogenetically identical with the long arm of In(6.15) in the variant IgK/myc translocations. This chromosome carried R-myc and IgK in juxtaposition, as indicated by comigration on pulsed field electrophoresis (PFGE). At stage IV, the R-myc carrying AKR-derived chromosome 15s were present in six copies. Possible relationships between the increasing R/G myc ratio and changed growth characteristics in vivo and in vitro are discussed.
|
|
| 39. |
- Jakobsson, Lotta, 1967, et al.
(författare)
-
Large animal crashes: The significance and challenges
- 2015
-
Ingår i: 2015 IRCOBI Conference Proceedings - International Research Council on the Biomechanics of Injury. ; , s. 302-314
-
Konferensbidrag (refereegranskat)abstract
- Crashes with large animals pose demands on vehicle design beyond standardised crash test methods. In some parts of the world, crashes with large animals are frequent and involve a relatively high risk of injury. The objective of this study is to identify the significance of the occurrence and the challenges of crashes with large animals, including evaluations using a crash test method simulating a vehicle-to-large animal crash. Statistics identify several important factors, such as impact speed, impact configuration, environmental factors and driver awareness. Occupant injuries of special focus are injuries to head, neck and upper extremities both by penetrating roof structure parts and by interaction with the large animal body, and cuts and scrapes by splintering glass or sharp edges. Tests using a large animal dummy illustrate the importance of structural integrity of the header and A-pillar area, as well as vehicle speed at impact. An increased impact speed not only drives the structural intrusion depth but also influences the timing of head impact towards the deformed area. As a complement to structural and restraint designs, future safety development challenges also include aspects of detecting and sensing large animals addressing occupant protection by mitigating and potentially avoiding the crash.
|
|
| 40. |
- Lycken, M., et al.
(författare)
-
Changes in Characteristics of Men with Lethal Prostate Cancer During the Past 25 Years: Description of Population-based Deaths
- 2022
-
Ingår i: European Urology Open Science. - Nederländerna : Elsevier BV. - 2666-1691 .- 2666-1683. ; 41, s. 81-87
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Attempts to reduce prostate cancer (PC) mortality require an understanding of temporal changes in the characteristics of men with lethal PC. Objective: To describe the diagnostic characteristics of and time trends for a nationwide population-based cohort of Swedish men who died from PC between 1992 and 2016. Design, setting, and participants: Men with PC as the underlying cause of death from 1992 to 2016 according to the Swedish Cause of Death Register were included in the study. Characteristics at diagnosis were collected via links to other nationwide registries using personal identity numbers. Outcome measurements and statistical analysis: Data on disease duration, age at death, and risk category were analyzed. Missing data for risk categories for men with an early date of PC diagnosis were imputed according to the method of chained equations. Results and limitations: Between 1992 and 2016, age-standardized PC mortality decreased by 25%. Median PC disease duration increased from 3.3 yr (interquartile range [IQR] 1.6-6.3) to 5.9 yr (IQR 2.5-10.3) and the median age at death from PC increased from 78.9 yr (IQR 73.3-84.2) to 82.2 yr (IQR 75.2-87.5). The proportion of men with localized disease at diagnosis who died from PC increased from 34% to 48%, while the rate of distant metastases at diagnosis decreased from 56% to 42%. The rate of distant metastases at diagnosis was highest among the youngest men. Treatment trajectories could not be described owing to the large proportion of missing data before the start of registration in the National Prostate Cancer Registry. Conclusion: Age-standardized PC mortality has decreased substantially since 1992. However, there is still a high proportion of men who die from PC who had localized disease at diagnosis, which indicates that more attention is needed to identify the underlying causes to prevent disease progression. Since the proportion of men with distant metastases at diagnosis remains high, early detection of lethal tumors is essential to further reduce PC mortality. Patient summary: We investigated the characteristics of men who died from prostate cancer in Sweden between 1992 and 2016. We found that men with lethal prostate cancer live longer and are older when they die today in comparison to men who died at the beginning of the study period. However, the proportion of men with distant metastases at diagnosis remains high, which is why early detection of lethal tumors is essential to reduce mortality. (C) 2022 The Author(s). Published by Elsevier B.V. on behalf of European Association of Urology.
|
|
| 41. |
- Lycken, Magdalena, et al.
(författare)
-
The use of palliative medications before death from prostate cancer: Swedish population-based study with a comparative overview of European data
- 2018
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 88, s. 101-108
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Symptoms of terminal cancer have previously been reported as under-treated. The aim of this study was to assess the use of palliative medications before death from prostate cancer. Methods: This Swedish register study included men who died from 2009 to 2012 with prostate cancer as the underlying cause of death. We assessed the proportion who collected a prescription of androgen deprivation therapy, non-steroidal anti-inflammatory drugs, paracetamol, opioids, glucocorticoids, antidepressants, anxiolytics and sedative-hypnotics and the differences in treatment related to age, time since diagnosis, educational level, close relatives and comorbidities. Data were collected from 3 years before death from prostate cancer. Results: We included 8326 men. The proportion who received opioids increased from 30% to 72% during the last year of life, and 67% received a strong opioid at the time of death. Antidepressants increased from 13% to 22%, anxiolytics from 9% to 27% and sedative-hypnotics from 21% to 33%. Men without close relatives and older men had lower probability to receive opioids (odds ratio [OR]: 0.56, 95% confidence interval [CI]: 0.47-0.66 for > 85 years versus < 70 years) and (OR 0.78, 95% CI: 0.66-0.92 for unmarried without children versus married with children). Conclusion: Our results represent robust epidemiological data from Sweden for comparison of palliative care quality between countries. The findings indicate that men without close relatives and older men are disadvantaged with respect to the treatment of cancer pain and need closer attention from health care providers and highlight the importance to identify psychological distress in terminal prostate cancer. (C) 2017 Elsevier Ltd. All rights reserved.
|
|
| 42. |
|
|
| 43. |
- Mestdagh, Pieter, et al.
(författare)
-
The miR-17-92 MicroRNA Cluster Regulates Multiple Components of the TGF-beta Pathway in Neuroblastoma
- 2010
-
Ingår i: Molecular Cell. - : Elsevier BV. - 1097-4164 .- 1097-2765. ; 40:5, s. 762-773
-
Tidskriftsartikel (refereegranskat)abstract
- The miR-17-92 microRNA cluster is often activated in cancer cells, but the identity of its targets remains elusive. Using SILAC and quantitative mass spectrometry, we examined the effects of activation of the miR-17-92 cluster on global protein expression in neuroblastoma (NB) cells. Our results reveal cooperation between individual miR-17-92 miRNAs and implicate miR-17-92 in multiple hallmarks of cancer, including proliferation and cell adhesion. Most importantly, we show that miR-17-92 is a potent inhibitor of TGF-beta signaling. By functioning both upstream and downstream of pSMAD2, miR-17-92 activation triggers downregulation of multiple key effectors along the TGF-beta signaling cascade as well as direct inhibition of TGF-beta-responsive genes.
|
|
| 44. |
- Ohlsson, Bodil, et al.
(författare)
-
Continuous infusion of cholecystokinin leads to down-regulation of the cholecystokinin-A receptor in the rat pancreas
- 2000
-
Ingår i: Scandinavian Journal of Gastroenterology. - : Informa UK Limited. - 1502-7708 .- 0036-5521. ; 35:6, s. 612-618
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Infusion of sulphated cholecystokinin-8 (CCK-8S) in rats transiently increased the proliferation of pancreatic acinar cells, whereas the CCK-A receptor antagonist devazepide decreased such proliferation. This effect ceased after 3 days. CCK-8S or devazepide injected twice daily induced a persistent effect on the cell proliferation involving the major cells of the exocrine pancreas. The aim of this study was to examine the effect of continuous infusion of CCK-8S and devazepide on CCK-A receptor gene expression. METHODS: Male Sprague-Dawley rats received subcutaneous continuous infusion of 5 microg/kg/h CCK-8S, 200 microg/kg/h devazepide, or 1% bovine serum albumin (BSA) by means of osmotic minipumps. The rats were killed after 4 days; I h before being killed they received 5-bromo-2-deoxyuridine (BrdU) intraperitoneally. Plasma was collected for analysis of CCK. The pancreas was dissected, and indirect immunofluorescence for BrdU and CCK-A receptor was performed. In situ hybridization to CCK-A receptor mRNA was performed for examination and semiquantification of receptor gene expression. RESULTS: Continuous infusion of CCK-8S led to a sixfold increase in plasma CCK and a 40% increase in pancreatic weight. Devazepide did not affect the CCK level but decreased the pancreatic weight by 24% compared with BSA-infused rats. The BrdU labeling indicated that CCK-8S had no effect on cell proliferation. Immunofluorescence for the CCK-A receptor showed a decreased labeling intensity after CCK-8S infusion. The mean optical density of in situ hybridization labeling of the sections from CCK-8S-treated rats was decreased to 37% +/- 3% of that in controls. Devazepide did not affect the CCK-A receptor gene expression. CONCLUSIONS: Continuous stimulation of the CCK-A receptor led to a downregulation of the receptor gene expression in pancreatic acinar cells and decreased labeling of the receptor at immunohistochemistry. The results suggest that down-regulation of the receptor is a protective mechanism against overstimulation.
|
|
| 45. |
- Persson, Bodil, 1950-, et al.
(författare)
-
Cardiovascular mortality among Swedish pulp and paper mill workers
- 2007
-
Ingår i: Am J Ind Med. - : Wiley. - 0271-3586 .- 1097-0274. ; 50:3, s. 221-6
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Malignant diseases but also cardiovascular and respiratory disorders and diabetes mellitus have been associated with work in pulp and paper production. The present cohort focuses on cardiovascular mortality in relation to various exposures in this industry. METHODS: The cohort, followed-up for mortality, includes 7,107 workers, 6,350 men and 757 women, from three major old mills in the middle of Sweden. RESULTS: Instead of a healthy-worker effect, a slightly increased risk for death in diseases of the circulatory system was found for male workers. Notably, work with sulfate digestion, steam and power generation and maintenance was associated with significantly increased risks. Cerebrovascular diseases showed non-significantly increased risks for maintenance and paper and paperboard production and manufacture. CONCLUSIONS: The differences in risk among various parts of the production are striking although it is hard to pinpoint any specific exposures. Dust and small particles along with sulfur compounds might be suspected.
|
|
| 46. |
- Press, R, et al.
(författare)
-
Autologous haematopoietic stem cell transplantation: a viable treatment option for CIDP
- 2014
-
Ingår i: Journal of Neurology, Neurosurgery and Psychiatry. - : BMJ. - 0022-3050 .- 1468-330X. ; 85:6, s. 618-624
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Only 70-80% of patients with chronic inflammatory demyelinating polyneuropathy (CIDP) respond satisfactorily to the established first-line immunomodulatory treatments. Autologous haematopoietic stem cell transplantation (AHSCT) has been performed as a last treatment resort in a few therapy-refractory cases with CIDP. We describe the results of AHSCT in 11 consecutive Swedish patients with therapy-refractory CIDP with a median follow-up time of 28 months. METHOD: Case data were gathered retrospectively for AHSCT treatments in 11 patients with CIDP refractory to the first-line immunomodulatory treatments, intravenous high-dose immunoglobulin, corticosteroids and plasma exchange and to one or more second-line treatments used in 10 of the 11 patients. RESULTS: The median Inflammatory Neuropathy Cause and Treatment (INCAT) score within 1 month prior to AHSCT was 6 and the Rankin score 4. Total INCAT and Rankin scores improved significantly within 2-6 months after AHSCT and continued to do so at last follow-up. The motor action potential amplitudes (CMAP) improved already within 4 months (median) after AHSCT. Three of the 11 patients relapsed during the follow-up period, requiring retransplantation with AHSCT in one. Eight of the 11 patients maintained drug-free remission upon last follow-up. AHSCT was safe but on the short term associated with a risk of cytomegalovirus (CMV) and Epstein-Barr virus reactivation, CMV disease, haemorrhagic cystitis and pancreatitis. CONCLUSIONS: Our results though hampered by the limited number of patients and the lack of a control group suggest AHSCT to be efficacious in therapy-refractory CIDP, with a manageable complication profile. Confirmation of these results is necessary through randomised controlled trials.
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
|
|
| 50. |
|
|
