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- Djerf, Emelie, 1980-
(författare)
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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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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)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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- Hansson, Thomas, et al.
(författare)
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Sights of touching activates the somatosensory cortex in humans
- 2009
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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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- Kokhaei, Parviz, et al.
(författare)
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Expression of erythropoietin receptor and in vitro functional effects of epoetins in B-cell malignancies
- 2007
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 13:12, s. 3536-3544
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Erythropoietin (EPO) and EPO receptor (EPO-R) expression have been reported in solid tumors and are claimed to regulate tumor growth; however, no data have been published on this issue in B-cell malignancies or normal lymphoid cells. This report describes genomic/protein EPO-R expression and in vitro effects of recombinant human EPO (epoetin) in B-cell chronic lymphocytic leukemia (B-CLL), mantle-cell lymphoma (MCL), and multiple myeloma (MM). Experimental Design: Blood samples were obtained from patients with B-CLL, MCL, and healthy volunteers, and bone marrow was obtained from MM patients. EPO-R mRNA was detected by reverse transcription-PCR. EPO-R surface expression was investigated by flow cytometry using digoxigenin-labeled epoetin and polyclonal rabbit anti–EPO-R antibody for intracellular receptor. Tumor cell stimulation was determined in vitro using [3H]thymidine incorporation and CD69 expression after exposure to epoetin α or β or darbepoetin α. Results: EPO-R mRNA was detected in mononuclear cells from 32 of 41 (78%) B-CLL and 5 of 7 (71%) MCL patients, and 21 of 21 (100%) MM samples. Expression was also detected in highly purified T cells from six of eight B-CLL patients, four of four MM patients, and normal donor B and T cells. Surface EPO-R protein was not detected. Intracellular EPO-R staining with anti–EPO-R antibodies was unspecific. No tumor-stimulatory effect was observed with high epoetin concentrations. Conclusions:EPO-R gene is frequently expressed in lymphoid malignancies and normal B and T cells. However, there was no surface protein expression and no epoetin-induced in vitro stimulation of tumor B cells, indicating that epoetin therapy in vivo is likely to be safe in patients with lymphoid malignancies.
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- Lundborg, Göran, et al.
(författare)
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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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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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