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- Svensson Månsson, Sofie, et al.
(författare)
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ERK phosphorylation is linked to VEGFR2 expression and Ets-2 phosphorylation in breast cancer and is associated with tamoxifen treatment resistance and small tumours with good prognosis
- 2005
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Ingår i: Oncogene. - Basingstoke : Macmillan Press. - 0950-9232 .- 1476-5594. ; 24:27, s. 4370-4379
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Tidskriftsartikel (refereegranskat)abstract
- Extracellular signal-regulated kinase (ERK)1/2 signalling mediates communication between growth factor receptors and the cell nucleus and has been linked to several key events in the transformation process such as proliferation and invasion. We therefore sought to delineate the degree of phosphorylated ERK1/2 in breast cancer and potential links to upstream receptors such as VEGFR2, ErbB2, downstream targets, such as Ets-2, as well as clinico-pathological parameters, clinical outcome and response to tamoxifen. ERK1/2 phosphorylation was assessed by immunohistochemistry using a phospho-specific ERK1/2 antibody in three breast cancer cohorts including a total of 886 tumours arranged in tissue arrays. Cohort I consisted of 114 patients, cohort II of 248 postmenopausal patients randomized to either 2 years of tamoxifen or no adjuvant treatment and cohort III of 524 patients. Surprisingly, ERK1/2 phosphorylation correlated inversely with tumour size. Phosphorylated ERK1/2 was further associated with the presence of VEGFR2 (cohorts II and III) and the degree of phosphorylated Ets-2, indicating in vivo, a signalling cascade from VEGFR2 via ERK1/2 to Ets-2 phosphorylation. Interestingly, ERK1/2 phosphorylation correlated with better survival in untreated patients independently of lymph-node status and tumour size indicating that ERK1/2 signalling might be associated with a less aggressive phenotype. Finally, patients with oestrogen receptor positive and ERK1/2 phosphorylated tumours also had an impaired tamoxifen response.
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| 4. |
- Ageberg, Eva, et al.
(författare)
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Principles of brain plasticity in improving sensorimotor function of the knee and leg in healthy subjects: A double-blind randomized exploratory trial
- 2009
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Ingår i: BMC Musculoskeletal Disorders. - : Springer Science and Business Media LLC. - 1471-2474. ; 10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Principles of brain plasticity is used in the treatment of patients with functional limitations to improve sensorimotor function. Training is included in the treatment of knee injury to improve both patient-reported function and sensorimotor function. However, impairment in sensorimotor function often persists despite training. Therefore, it was suggested that training programs need to be more effective to improve sensorimotor function after knee injury. The aim of the current study was to investigate if principles of brain plasticity that have been successfully used on the hand and foot to improve sensorimotor function can be applied on the knee. We hypothesized that temporary anesthesia of the skin area above and below the knee would improve sensorimotor function of the ipsilateral knee and leg. Methods: In this first double-blind exploratory study, 28 uninjured subjects (mean age 26 years, range 19-34, 50% women) were randomized to temporary local cutaneous application of anesthetic (EMLA (R)) (n=14) or placebo cream (n=14). Fifty grams of EMLA, or placebo, was applied on the leg 10 cm above and 10 cm below the center of patella, leaving the area around the knee without cream. Measures of sensory function (perception of touch, vibration sense, knee kinesthesia) and motor function (knee muscle strength, hop test) were assessed before and after 90 minutes of treatment with EMLA or placebo. The paired t-test was used for comparisons within groups and the independent t-test for comparisons between groups. The number of subjects needed was determined by an a priori sample size calculation. Results: No statistically significant or clinically relevant differences were seen over time (before vs. after) in the measures of sensory or motor functions in the EMLA group or in the placebo group. There were no differences between the groups due to treatment effect (EMLA vs. placebo). Conclusion: We found no effect of temporary cutaneous anesthesia on sensorimotor function of the ipsilateral knee and leg in uninjured subjects. The principles used in this study remain to be tested in subjects with knee injury.
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| 5. |
- Andersson, Ulrika, et al.
(författare)
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MNS16A minisatellite genotypes in relation to risk of glioma and meningioma and to glioblastoma outcome.
- 2009
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 125:4, s. 968-972
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Tidskriftsartikel (refereegranskat)abstract
- The human telomerase reverse transcriptase (hTERT) gene is upregulated in a majority of malignant tumours. A variable tandem repeat, MNS16A, has been reported to be of functional significance for hTERT expression. Published data on the clinical relevance of MNS16A variants in brain tumours have been contradictory. The present population-based study in the Nordic countries and the United Kingdom evaluated brain-tumour risk and survival in relation to MNS16A minisatellite variants in 648 glioma cases, 473 meningioma cases and 1,359 age, sex and geographically matched controls. By PCR-based genotyping all study subjects with fragments of 240 or 271 bp were judged as having short (S) alleles and subjects with 299 or 331 bp fragments as having long (L) alleles. Relative risk of glioma or meningioma was estimated with logistic regression adjusting for age, sex and country. Overall survival was analysed using Kaplan-Meier estimates and equality of survival distributions using the log-rank test and Cox proportional hazard ratios. The MNS16A genotype was not associated with risk of occurrence of glioma, glioblastoma (GBM) or meningioma. For GBM there were median survivals of 15.3, 11.0 and 10.7 months for the LL, LS and SS genotypes, respectively; the hazard ratio for having the LS genotype compared with the LL was significantly increased HR 2.44 (1.56-3.82) and having the SS genotype versus the LL was nonsignificantly increased HR 1.46 (0.81-2.61). When comparing the LL versus having one of the potentially functional variants LS and SS, the HR was 2.10 (1.41-3.1). However, functionality was not supported as there was no trend towards increasing HR with number of S alleles. Collected data from our and previous studies regarding both risk and survival for the MNS16A genotypes are contradictory and warrant further investigations.
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| 7. |
- Berglund, Mattias, et al.
(författare)
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Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma
- 2007
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952 .- 1530-0285. ; 20:1, s. 63-75
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Tidskriftsartikel (refereegranskat)abstract
- Follicular lymphoma is commonly transformed to a more aggressive diffuse large B-cell lymphoma (DLBCL). In order to molecularely characterize this histiological and clinical transformation, comparative genomic hybridization was applied on 23 follicular lymphoma and 35 transformed DLBCL tumors from a total of 30 patients. The results were also compared with our published findings in de novo DLBCL. Copy number changes were detected in 70% of follicular lymphoma and in 97% of transformed DLBCL. In follicular lymphoma, the most common alterations were +18q21 (33%), +Xq25–26 (28%), +1q31–32 (23%), and -17p (23%), whereas transformed DLBCL most frequently exhibited +Xq25–26 (36%), +12q15 (29%), +7pter-q22 (25%), +8q21 (21%), and -6q16–21(25%). Transformed DLBCL showed significantly more alterations as compared to follicular lymphoma (P=0.0001), and the alterations -6q16–21 and +7pter-q22 were only found in transformed DLBCL but not in follicular lymphoma (P=0.02). Alterations involving +13q22 were significantly less frequent, whereas -4q13–21 was more common in transformed as compared to de novo DLBCL (P=0.01 and P=0.02, respectively). Clinical progression from follicular lymphoma to transformed DLBCL is on the genetic level associated with acquirement of increasing number of genomic copy number changes, with non-random involvement of specific target regions. The findings support diverse genetic background between transformed and de novo DLBCL.
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