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Search Results: 1 - 10 of 412864 matches for " M?rten Fern? "
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RNA quality in frozen breast cancer samples and the influence on gene expression analysis – a comparison of three evaluation methods using microcapillary electrophoresis traces
Carina Strand, Johan Enell, Ingrid Hedenfalk, Mrten Fern
BMC Molecular Biology , 2007, DOI: 10.1186/1471-2199-8-38
Abstract: Comparing the methods pair-wise, Manual vs. Ratio showed concordance (good vs. degraded RNA) in 20/24, Manual vs. RIN in 23/24, and Ratio vs. RIN in 21/24 samples. All three methods were concordant in 20/24 samples. The comparison between RNA quality and gene expression analysis showed that pieces from the same tumor and with good RNA quality clustered together in most cases, whereas those with poor quality often clustered apart. The number of samples clustering in an unexpected manner was lower for the Manual (n = 1) and RIN methods (n = 2) as compared to the Ratio method (n = 5).Assigning the data into two groups, RIN ≥ 6 or RIN < 6, all but one of the top ten differentially expressed genes showed decreased expression in the latter group; i.e. when the RNA became degraded. Ontological mapping using GoMiner (p ≤ 0.05; ≥ 3 genes changed) revealed deoxyribonuclease activity, collagen, regulation of cell adhesion, cytosolic ribosome, and NADH dehydrogenase activity, to be the five categories most affected by RNA quality.The results indicate that the Manual and RIN methods are superior to the Ratio method for evaluating RNA quality in fresh frozen breast cancer tissues. The objective measurement when using the RIN method is an advantage. Furthermore, the inclusion of samples with degraded RNA may profoundly affect gene expression levels.The development of high-throughput technologies such as microarrays, allowing for the parallel analysis of the expression of thousands of genes from a tumor in one single experiment, has provided new tumor biological knowledge. In breast cancer, for example, microarrays have been suggested to be useful for predicting clinical outcome and for tailoring treatment strategies for individual patients [1-3]. This approach may also increase the ability to identify new targets for more specific therapies. Studies using this technique have furthermore revealed differences in gene expression profiles between different subgroups of breast cancer,
Prediction of outcome after diagnosis of metachronous contralateral breast cancer
Sara Alkner, P?r-Ola Bendahl, Mrten Fern, Jonas Manjer, Lisa Rydén
BMC Cancer , 2011, DOI: 10.1186/1471-2407-11-114
Abstract: Information on patient-, tumour-, treatment-characteristics, and outcome was abstracted from patients' individual charts for all patients diagnosed with metachronous CBC in the Southern Healthcare Region of Sweden from 1977-2007. Distant disease-free survival (DDFS) and risk of distant metastases were primary endpoints.The cohort included 723 patients with metachronous contralateral breast cancer as primary breast cancer event. Patients with less than three years to BC2 had a significantly impaired DDFS (p = 0.01), and in sub-group analysis, this effect was seen primarily in patients aged <50. By logistic regression analysis, patients diagnosed with BC2 within routine follow-up examinations had a significantly lower risk of developing metastases compared to those who were symptomatic at diagnosis (p < 0.0001). Chemotherapy given after breast BC1 was a negative prognostic factor for DDFS, whereas endocrine treatment and radiotherapy given after BC2 improved DDFS.In a large cohort of patients with CBC, we found the time interval to BC2 to be a strong prognostic factor for DDFS in young women and mode of detection to be related to risk of distant metastases. Future studies of tumour biology of BC2 in relation to prognostic factors found in the present study can hopefully provide biological explanations to these findings.Within their lifetime, 2-20% of breast cancer patients develop a new tumour in their contralateral breast [1-3]. These contralateral breast cancers (CBC) are called synchronous if the second tumour (BC2) develops within a short time interval from the first tumour (BC1), and metachronous if the time interval between tumours is longer. In line with several previous studies, we define metachronous tumours as CBC diagnosed at least three months after BC1 [3-5]. However, a clear cut-off time is not defined in the literature. CBC is today treated as a new primary tumour (two individual tumours), but the biological relationship between BC1 and BC2, and the imp
Expression profiling to predict outcome in breast cancer: the influence of sample selection
Sofia K Gruvberger, Markus Ringnér, Patrik Edén, ?ke Borg, Mrten Fern, Carsten Peterson, Paul S Meltzer
Breast Cancer Research , 2002, DOI: 10.1186/bcr548
Abstract: Recent studies have shown that microarray analysis of tumors generate molecular phenotypes that can be used to classify tumors into subgroups that are not evident by traditional histopathological methods, to improve diagnosis, and to predict outcomes of disease [1-6]. In a recent study, van 't Veer et al. [7] reported, among other important conclusions, that expression profiles of sporadic primary breast tumors could be used to predict disease recurrence better than currently available clinical and histopathological prognostic factors (i.e. tumor grade, tumor size, angioinvasion, age, and estrogen receptor [ER]-α). Those investigators identified a set of 231 genes, from which they extracted 70 that were used to predict recurrences within 5 years with an accuracy of 89% for a test set of 20 tumors. However, our experience suggests that, in breast cancer patient populations, predicting clinical variables from gene expression data is complicated by a common correlation between ER-α status and the clinical parameters studied. ER-α status has been shown to leave a remarkable imprint on the expression profile of a tumor, and may have confounding effects on the clinical factor studied [7-9]. Therefore, we believe that it is necessary to be cautious when interpreting the results from the study of van 't Veer et al. and similar studies.In the set of tumors analyzed by Van't Veer et al. [7] there is an evident correlation between clinical outcome for the patients and ER-α status of the tumors. For that reason, we investigated whether their results can be applied to a data set from a different patient cohort in which there is no correlation between ER-α status and prognosis.ER-α status is by far the most obvious and noticeable subdivision of breast tumors based on gene expression profiles. This has become evident in several studies [4,7-9]. In a previous study [8] we used the gene expression profiles of 47 tumors and artificial neural networks to generate a prediction model ba
Field triage in trauma – do the data really justify the conclusions?
Mrten Sandberg
Scandinavian Journal of Trauma, Resuscitation and Emergency Medicine , 2009, DOI: 10.1186/1757-7241-17-24
Abstract: I read with interest the recently published paper by Rehn and coworkers about field triage in trauma [1]. The topic is interesting and improved quality of the work and information flow from the scene-of-the-accident to the emergency department can save lives. However, some of the conclusions drawn by the authors can be challenged.First, the authors compared undertriage and overtriage of the traumatized patients and found 2% and 17% undertriage and 35% and 66% overtriage for anaesthetists and paramedics, respectively. They conclude that "anaesthetists perform precise trauma triage, whereas paramedics have potential for improvement" although the authors themselves state that "skewed mission profiles make comparison of differences in triage precision difficult" [1]. The ground ambulances staffed with paramedics are used locally while the helicopters staffed with anaesthetists are a regional resource. The helicopters are dispatched when major trauma is suspected while ground ambulances are dispatched to any sort of incidence. In Oslo, an anaesthetist-staffed ground ambulance operates alongside ordinary ambulances and the patients transported with this service are a subgroup of the patients transported by anaesthetists. If the triage precision between paramedics and anaesthetists is to be compared, data from ground ambulances in Oslo (with or without anaesthetist) should be used and the data from patients brought to the hospital by helicopter or other services should be excluded. Such a comparison would give a good indication about the real difference in triage precision between the two groups of prehospital care providers. Unfortunately, that subgroup analysis has not been performed. That is sad, because the numbers that is provided in the article is of little interest since the services that are compared are too different.Second, in the system described, the paramedics or the anaesthetists examine the patient and investigate the mechanism of the accident before reporti
A Result for Orthogonal Plus Rank-1 Matrices
Mrten Wadenb?ck
Mathematics , 2015,
Abstract: In this paper the sum of an orthogonal matrix and an outer product is studied, and a relation between the norms of the vectors forming the outer product and the singular values of the resulting matrix is presented. The main result may be found in Theorem 1.
Tiling array-CGH for the assessment of genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs
Sara Brommesson, G?ran J?nsson, Carina Strand, Dorthe Grabau, Per Malmstr?m, Markus Ringnér, Mrten Fern, Ingrid Hedenfalk
BMC Clinical Pathology , 2008, DOI: 10.1186/1472-6890-8-6
Abstract: 32 K tiling microarray-based comparative genomic hybridization (aCGH) was used to explore the genomic similarities among synchronous unilateral and bilateral invasive breast cancer tumor pairs, and was compared with histopathological and tumor biological parameters.Based on global copy number profiles and unsupervised hierarchical clustering, five of ten (p = 1.9 × 10-5) unilateral tumor pairs displayed similar genomic profiles within the pair, while only one of eight bilateral tumor pairs (p = 0.29) displayed pair-wise genomic similarities. DNA index, histological type and presence of vessel invasion correlated with the genomic analyses.Synchronous unilateral tumor pairs are often genomically similar, while synchronous bilateral tumors most often represent individual primary tumors. However, two independent unilateral primary tumors can develop synchronously and contralateral tumor spread can occur. The presence of an intraductal component is not informative when establishing the independence of two tumors, while vessel invasion, the presence of which was found in clustering tumor pairs but not in tumor pairs that did not cluster together, supports the clustering outcome. Our data suggest that genomically similar unilateral tumor pairs may represent a more aggressive disease that requires the addition of more severe treatment modalities, and underscores the importance of evaluating the clonality of multiple tumors for optimal patient management. In summary, our findings demonstrate the importance of evaluating the properties of both tumors in order to determine the most optimal patient management.The incidence of synchronous bilateral breast cancer is low, corresponding to less than 2% of all breast cancer diagnoses [1-3]. The definition of synchronism in this context is, however, ambiguous in the literature, and the time spans used to define breast cancers as synchronous range from one month to two years, making the interpretation of incidence difficult [4-6]. In
The Three Receptor Tyrosine Kinases c-KIT, VEGFR2 and PDGFRα, Closely Spaced at 4q12, Show Increased Protein Expression in Triple-Negative Breast Cancer
Sara Jansson, P?r-Ola Bendahl, Dorthe Aamand Grabau, Anna-Karin Falck, Mrten Fern, Kristina Aaltonen, Lisa Rydén
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0102176
Abstract: Background Triple-negative breast cancer (TNBC) is a heterogeneous subgroup of breast cancer with poor prognosis and no targeted therapy available. Receptor tyrosine kinases (RTKs) are emerging targets in anticancer therapy and many RTK-inhibiting drugs are currently being developed. The aim of this study was to elucidate if there is a correlation between the protein expression of three RTKs c-KIT, VEGFR2 and PDGFRα, their gene copy number, and prognosis in TNBC compared to non-TNBC. Methods Tumor tissue samples from patients diagnosed with primary breast cancer were stained with immunohistochemistry (IHC) for protein assessment, and with fluorescence in situ hybridization (FISH) for gene copy number determination. Breast cancer mortality (BCM), measured from the date of surgery to death, was used as endpoint. Results The cohort included 464 patients, out of which 34 (7.3%) had a TNBC. High expression of the three RTKs was more common in TNBC compared to non-TNBC: c-KIT 49% vs. 10% (P<0.001), PDGFRα 32% vs. 19% (P = 0.07) and VEGFR2 32% vs. 6% (P<0.001). The odds ratio (OR) of c-KIT, VEGFR2 and PDGFRα positivity, adjusted for tumor characteristics, was 6.8, 3.6 and 1.3 times higher for TNBC than for non-TNBC. 73.5% of the TNBC had high expression of at least one of the three investigated receptors, compared to 30.0% of the non-TNBC (P<0.001). Survival analysis showed no significant difference in BCM for TNBC patients with high vs. low c-KIT, PDGFRα or VEGFR2 protein expression. 193 (42%) tumors were evaluated with FISH. No correlation was seen between increased gene copy number and TNBC, or between increased gene copy number and high protein expression of the RTK. Conclusion c-KIT, VEGFR2 and PDGFRα show higher protein expression in TNBC compared to non-TNBC. Further investigation clarifying the importance of these RTKs in TNBC is encouraged, as they are possible targets for anticancer therapy.
Selectivity in the Reinnervation of the Lateral Gastrocnemius Muscle after Nerve Repair with Ethyl Cyanoacrylate in the Rat
Thomas Landegren,Mrten Risling
Frontiers in Neurology , 2011, DOI: 10.3389/fneur.2011.00025
Abstract: There is a need for complementary surgical techniques that enable rapid and reliable primary repair of transected nerves. Previous studies after peripheral nerve transection and repair with synthetic adhesives have demonstrated regeneration to an extent comparable to that of conventional techniques. The aim of this study was to compare two different repair techniques on the selectivity of muscle reinnervation after repair and completed regeneration. We used the cholera toxin B technique of retrograde axonal tracing to evaluate the morphology, the number, and the three-dimensional location of α-motoneurons innervating the lateral gastrocnemius muscle and compared the results after repair with either ethyl cyanoacrylate (ECA) or epineural sutures of the transected parent sciatic nerve. In addition, we recorded the wet weight of the muscle. Six months after transection and repair of the sciatic nerve, the redistribution of the motoneuron pool was markedly disorganized, the motoneurons had apparently increased in number, and they were scattered throughout a larger volume of the spinal cord gray matter with a decrease in the synaptic coverage compared to controls. A reduction in muscle weight was observed as well. No difference in morphometric variables or muscle weight between the two repair methods could be detected. We conclude that the selectivity of motor reinnervation following sciatic nerve transection and subsequent repair with ECA is comparable to that following conventional micro suturing.
Invariant star-products on S^2 and the canonical trace
Keizo Matsubara,Mrten Stenmark
Mathematics , 2004, DOI: 10.1007/s11005-004-4290-7
Abstract: In the literature there are two different ways of describing an invariant star product on $S^2$. We show that the products are actually the same. We also calculate the canonical trace and use the Fedosov-Nest-Tsygan index theorem to obtain the characteristic class of this product.
Gene expression profiling in primary breast cancer distinguishes patients developing local recurrence after breast-conservation surgery, with or without postoperative radiotherapy
Emma Niméus-Malmstr?m, Morten Krogh, Per Malmstr?m, Carina Strand, Irma Fredriksson, Per Karlsson, Bo Nordenskj?ld, Olle St?l, G?rel ?stberg, Carsten Peterson, Mrten Fern
Breast Cancer Research , 2008, DOI: 10.1186/bcr1997
Abstract: We performed gene expression analysis (oligonucleotide arrays, 26,824 reporters) on 143 patients with lymph node-negative disease and tumor-free margins. A support vector machine was employed to build classifiers using leave-one-out cross-validation.Within the estrogen receptor-positive (ER+) subgroup, the gene expression profile clearly distinguished patients with local recurrence after radiotherapy (n = 20) from those without local recurrence (n = 80 with or without radiotherapy). The receiver operating characteristic (ROC) area was 0.91, and 5,237 of 26,824 reporters had a P value of less than 0.001 (false discovery rate = 0.005). This gene expression profile provides substantially added value to conventional clinical markers (for example, age, histological grade, and tumor size) in predicting local recurrence despite radiotherapy. Within the ER- subgroup, a weaker, but still significant, signal was found (ROC area = 0.74). The ROC area for distinguishing patients who develop local recurrence from those who remain local recurrence-free in the absence of radiotherapy was 0.66 (combined ER+/ER-).A highly distinct gene expression profile for patients developing local recurrence after breast-conservation surgery despite radiotherapy has been identified. If verified in further studies, this profile might be a most important tool in the decision making for surgery and adjuvant therapy.The addition of postoperative radiotherapy to breast-conservation surgery in patients with lymph node-negative breast cancer has been shown to reduce the 10-year risk of local recurrence from 29.2% to 10% [1]. However, more than half of the patients will never develop local recurrence whether given radiotherapy or not and a small proportion of the patients will develop local recurrence despite being given radiotherapy. Besides tumor-involved margins, generally accepted risk factors for the development of local recurrence are young age and multicentricity [2-5]. A number of other risk fact
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