| 1. |
- Djerf, Emelie, 1980-
(author)
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Studies on the effect of ErbB tyrosine kinase inhibitors on malignant melanoma growth and survival in vitro
- 2009
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Licentiate thesis (other academic/artistic)abstract
- Malignant melanoma has one of the fastest increasing incidences among the different types of cancerin the Western world. This raise can partly be ascribed to the change in sun habits that has takenplace during the last decades, since the major external risk factor for melanoma is exposure toultraviolet radiation. Patients with early stages of melanoma can often be cured by surgery, howeverfor patients suffering from metastatic melanoma there are only a few treatment options available.Unfortunately malignant melanoma is often resistant to radio-, bio- and chemotherapy and treatmentwith the currently most frequently used agent, dacarbazine, is characterized by a very low clinicalresponse rate. Therefore, there is an urgent need for new treatment strategies which can increase theoverall survival and cause less severe side effects.The aim of this thesis was to investigate the anti-tumor effect of two different tyrosine kinaseinhibitors (TKIs), gefitinib and canertinib, on two different human malignant melanoma (RaH3 andRaH5) cell lines. We investigate the effect of these two drugs on cell proliferation and survival andstudied the effect of gefitinib and canertinib on ErbB1-4 receptor phosphorylation, as well as Akt,Erk1/2 and Stat3 activity.Our results showed that phosphorylation of ErbB1, ErbB2 and ErbB3 decreased followingtreatment with both gefitinib and canertinib and that the subsequent downstream signaling via Akt,Erk1/2 and Stat3 was inhibited after TKI treatment. However, it was noted that the gefitinibinducedinhibition of Akt, and particularly Erk1/2, was transient and only a weak inhibition of Stat3phosphorylation was seen. Gefitinib treatment of the RaH3 and RaH5 cells resulted in anaccumulation of the cells in the G1 phase of the cell cycle without any induction of apoptosis.Canertinib caused a more pronounced inhibition of Akt, Erk1/2, and Stat3 phosphorylation thangefitinib. This might be one explanation to why canertinib induced apoptosis in RaH3 and RaH5cells whereas gefitinib only caused cell cycle arrest. In conclusion, gefitinib and canertinib displaypromising anti-tumor effects on ErbB expressing malignant melanoma and might be used in futurestudies in combination with conventional chemotherapy or other targeted therapies in the treatmentof malignant melanoma.
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| 2. |
- Fornander, Lotta, et al.
(author)
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Age- and time-dependent effects on functional outcome and cortical activation pattern in patients with median nerve injury: a functional magnetic resonance imaging study Clinical article
- 2010
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In: Journal of Neurosurgery. - : American Association of Neurological Surgeons. - 0022-3085 .- 1933-0693. ; 113:1, s. 122-128
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Journal article (peer-reviewed)abstract
- Object. The authors conducted a study to determine age- and time-dependent effects on the functional outcome after median nerve injury and repair and how such effects are related to changes in the pattern of cortical activation in response to tactile stimulation of the injured hand. Methods. The authors studied 11 patients with complete unilateral median nerve injury at the wrist repaired with epineural suture. In addition, 8 patients who were reported on in a previous study were included in the statistical analysis. In the entire study cohort, the mean age at injury was 23.3 +/- 13.4 years (range 7-57 years) and the time after injury ranged from 1 to 11 years. Sensory perception was measured with the static 2-point discrimination test and monofilaments. Functional MR imaging was conducted during tactile stimulation (brush strokes) of Digits II-III and IV-V of both hands, respectively. Results. Tactile sensation was diminished in the median territory in all patients. The strongest predictor of 2-point discrimination was age at injury (p less than 0.0048), and when this was accounted for in the regression analysis, the other age- and time-dependent predictors had no effect. The activation ratios (injured/healthy hand) for Digit II-III and Digit IV-V stimulation were positively correlated (rho 0.59, p less than 0.011). The activation ratio for Digit II-III stimulation correlated weakly with time after injury (p less than 0.041). The activation ratio of Digits IV-V correlated weakly with both age at injury (p less than 0.048) and time after injury (p less than 0.033), but no predictor reached significance in the regression model. The mean ratio of ipsi- and contralateral hemisphere activation after stimulation of the injured hand was 0.55, which was not significantly different from the corresponding ratio of the healthy hand (0.66). Conclusions. Following a median nerve injury (1-11 years after injury) there may be an initial increase in the volume of the cortical representation, which subsequently declines during the restoration phase. These dynamic changes may involve both median and ulnar nerve cortical representation, because both showed negative correlation with time after injury. These findings are in agreement with animal studies showing that cortical plasticity is an important mechanism for functional recovery after peripheral nerve injury and repair.
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| 3. |
- Fornander, Lotta, et al.
(author)
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Cortical plasticity in patients with median nerve lesions studied with MEG
- 2016
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In: Somatosensory & motor research. - : TAYLOR & FRANCIS LTD. - 0899-0220 .- 1369-1651. ; 33:3-4, s. 178-185
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Journal article (peer-reviewed)abstract
- We have previously shown age- and time-dependent effects on brain activity in the primary somatosensory cortex (SI), in a functional magnetic resonance imaging (fMRI) study of patients with median nerve injury. Whereas fMRI measures the hemodynamic changes in response to increased neural activity, magnetoencephalography (MEG) offers a more concise way of examining the evoked response, with superior temporal resolution. We therefore wanted to combine these imaging techniques to gain additional knowledge of the plasticity processes in response to median nerve injury. Nine patients with median nerve trauma at the wrist were examined with MEG. The N1 and P1 responses at stimulation of the injured median nerve at the wrist were lower in amplitude compared to the healthy side (pamp;lt;.04). Ulnar nerve stimulation of the injured hand resulted in larger N1 amplitude (pamp;lt;.04). The amplitude and latency of the response did not correlate with the sensory discrimination ability. There was no correlation between N1 amplitude and size of cortical activation in fMRI. There was no significant difference in N1 latency between the injured and healthy median nerve. N1 latency correlated positively with age in both the median and ulnar nerve, and in both the injured and the healthy hand (pamp;lt;.02 or pamp;lt;.001). It is concluded that conduction failure in the injured segment of the median nerve decreases the amplitude of the MEG response. Disinhibition of neighboring cortical areas may explain the increased MEG response amplitude to ulnar nerve stimulation. This can be interpreted as a sign of brain plasticity.
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| 4. |
- Fornander, Lotta, et al.
(author)
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Inter-hemispheric plasticity in patients with median nerve injury
- 2016
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In: Neuroscience Letters. - : Elsevier. - 0304-3940 .- 1872-7972. ; 628, s. 59-66
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Journal article (peer-reviewed)abstract
- Peripheral nerve injuries result in reorganization within the contralateral hemisphere. Furthermore, recent animal and human studies have suggested that the plastic changes in response to peripheral nerve injury also include several areas of the ipsilateral hemisphere. The objective of this study was to map the inter-hemispheric plasticity in response to median nerve injury, to investigate normal differences in contra- and ipsilateral activation, and to study the impact of event-related or blocked functional magnetic resonance imaging (fMRI) design on ipsilateral activation. Four patients with median nerve injury at the wrist (injured and epineurally sutured amp;gt;2 years earlier) and ten healthy volunteers were included. 3T fMRI was used to map the hemodynamic response to brain activity during tactile stimulation of the fingers, and a laterality index (LI) was calculated. Stimulation of Digits II-III of the injured hand resulted in a reduction in contralateral activation in the somatosensory area SI. Patients had a lower LI (0.21 +/- 0.15) compared to healthy controls (0.60 +/- 0.26) indicating greater ipsilateral activation of the primary somatosensory cortex. The spatial dispersion of the coordinates for areas SI and SII was larger in the ipsilateral than in the contralateral hemisphere in the healthy controls, and was increased in the contralateral hemisphere of the patients compared to the healthy controls. There was no difference in LI between the event-related and blocked paradigms. In conclusion, patients with median nerve injury have increased ipsilateral SI area activation, and spatially more dispersed contralateral SI activation during tactile stimulation of their injured hand. In normal subjects ipsilateral activation has larger spatial distribution than the contralateral. Previous findings in patients performed with the blocked fMRI paradigm were confirmed. The increase in ipsilateral SI activation may be due to an interhemispheric disinhibition associated with changes in the afferent signal inflow to the contralateral primary somatosensory cortex.
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| 5. |
- Hansson, Thomas, et al.
(author)
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Sights of touching activates the somatosensory cortex in humans
- 2009
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In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 1651-2073 .- 0284-4311. ; 43:5, s. 267-269
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Journal article (peer-reviewed)abstract
- We report our observations of cross-modal interactions between sight and touch using functional magnetic resonance imaging (fMRI). Experiments were devised to show that sight and touch are linked in a cross-modal arrangement, and two separate experiments were done in an MRI scanner. In the first, the subject's right hand was stimulated with a brush; in the second, a video sequence was presented to the subject inside the scanner through video goggles in visual three-dimensional stereo, showing one brushstroke every second on a hand in the same manner as the subject had just previously experienced. The result was that both the primary and the secondary somatosensory cortexes were activated in the participants when the hands were touched, and when the subjects saw only a hand being touched in the same manner. The results indicated cross-modal links between sight and touch of the hand in humans.
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| 6. |
- Johansson, Håkan, 1972-, et al.
(author)
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Characterization of Campylobacter spp. isolated from wild birds in the Antarctic and Sub-Antarctic
- 2018
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In: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 13:11
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Journal article (peer-reviewed)abstract
- A lack of knowledge of naturally occurring pathogens is limiting our ability to use the Antarctic to study the impact human-mediated introduction of infectious microorganisms have on this relatively uncontaminated environment. As no large-scale coordinated effort to remedy this lack of knowledge has taken place, we rely on smaller targeted efforts to both study present microorganisms and monitor the environment for introductions. In one such effort, we isolated Campylobacter species from fecal samples collected from wild birds in the Antarctic Peninsula and the sub-Antarctic island of South Georgia. Indeed, in South Georgia, we found Campylobacter lari and the closely related Campylobacter peloridis, but also distantly related human-associated multilocus sequence types of Campylobacter jejuni. In contrast, in the Antarctic Peninsula, we found C. tart and two closely related species, Campylobacter subantarcticus and Campylobacter volucris, but no signs of human introduction. In fact, our finding of human-associated sequence types of C. jejuni in South Georgia, but not in the Antarctic Peninsula, suggests that efforts to limit the spread of infectious microorganisms to the Antarctic have so far been successful in preventing the introduction of C. jejuni. However, we do not know how it came to South Georgia and whether the same mode of introduction could spread it from there to the Antarctic Peninsula.
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| 7. |
- Lundborg, Göran, et al.
(author)
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Artificial sensibility of the hand based on cortical audiotactile interaction : A study using functional magnetic resonance imaging
- 2005
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In: Scandinavian Journal of Plastic and Reconstructive Surgery and Hand Surgery. - : Informa UK Limited. - 0284-4311 .- 1651-2073. ; 39:6, s. 370-372
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Journal article (peer-reviewed)abstract
- The capacity of the central nervous system for plastic alterations is the base for our ability to adapt to environmental needs. The crossmodal capacity of the brain makes interaction between senses possible, and deprivation of one sense leads to compensatory changes in other senses. We have recently shown how hearing can substitute for sensation in a transplanted insensitive hand by using a sensor glove equipped with small microphones that pick up the sound of friction, which is elicited by active touch. Here we have used functional magnetic resonance imaging (fMRI) in healthy people to illustrate their capacity for cortical audiotactile interaction with activation of the somatosensory cortex induced by auditory stimuli. The phenomenon occurred only in subjects trained to substitute sensibility by hearing, and no audiotactile interaction was found in untrained subjects. © 2005 Taylor & Francis.
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| 8. |
- Mattsson, Agnes, et al.
(author)
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Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia : A Swedish nation-wide real-world report on consecutively identified patients
- 2023
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In: European Journal of Haematology. - : John Wiley & Sons. - 0902-4441 .- 1600-0609. ; 111:5, s. 715-721
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Journal article (peer-reviewed)abstract
- ObjectivesWe examined the efficacy and toxicity of the PI3Kδ inhibitor idelalisib in combination with rituximab salvage therapy in consecutively identified Swedish patients with chronic lymphocytic leukemia (CLL).Methods and ResultsThirty-seven patients with relapsed/refractory disease were included. The median number of prior lines of therapy was 3 (range 1–11); the median age was 69 years (range 50–89); 22% had Cumulative Illness Rating Scale (CIRS) >6 and 51% had del(17p)/TP53 mutation. The overall response rate was 65% (all but one was partial response [PR]). The median duration of therapy was 9.8 months (range 0.9–44.8). The median progression-free survival was 16.4 months (95% CI: 10.4–26.3) and median overall survival had not been reached (75% remained alive at 24 months of follow-up). The most common reason for cessation of therapy was colitis (n = 8, of which seven patients experienced grade ≥3 colitis). The most common serious adverse event was grade ≥3 infection, which occurred in 24 patients (65%).ConclusionsOur real-world results suggest that idelalisib is an effective and relatively safe treatment for patients with advanced-stage CLL when no other therapies exist. Alternative dosing regimens and new PI3K inhibitors should be explored, particularly in patients who are double-refractory to inhibitors of BTK and Bcl-2.
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| 9. |
- Norin, Stefan, et al.
(author)
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Severe infusion-related reactions are uncommon in rituximab-treated CLL patients in clinical practice: Results from a Swedish national observational study
- 2015
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In: Leukemia Research. - : Elsevier. - 0145-2126 .- 1873-5835. ; 39:1, s. 33-37
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Journal article (peer-reviewed)abstract
- There have been concerns about serious infusion-related adverse drug reactions (ADR) with rituximabin chronic lymphocytic leukemia (CLL). We therefore conducted an observational trial in which CLL patients planned for rituximab-containing therapy were eligible. Ninety-six patients from 19 centers were enrolled. The most common regimen was rituximab, fludarabine and cyclophosphamide. Fifty-six patients experienced ADR during rituximab infusion. Reactions greater than= grade 3 occurred in five patients and no cases of tumor lysis syndrome were recorded. Despite a high number of circulating tumor cells few severe ADR were noted. Thus, rituximab containing regimens can be considered safe for CLL patients in general practice.
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| 10. |
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