| 1. |
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| 2. |
- Zhou, Lihua
(författare)
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Perceived growth following gynecological cancer and its associated factors from the perspectives of Chinese women, spouses, couples and registered nurses
- 2023
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Gynecological cancer (GC) is the most common cancer diagnosis among women, globally, including China. Women who experience a diagnosis of GC, their spouses, the couples as a unit, as well as registered nurses (RNs) caring for these women, all face different challenges during this cancer trajectory. Prior to this study, few studies have explored the factors associated with perceived growth among women diagnosed with GC, their spouses, and couples, as well as RNs caring for these women, based on a growth-related theory and model. The overall aim of this thesis was therefore to explore perceived growth and its associated factors, based on these persons’ perspectives.Four studies (Study I–IV) ) were conducted, each using a cross-sectional and descriptive study design. In Study I, women’s posttraumatic growth (PTG) and its associated factors were explored. Data were collected through 344 questionnaires and analyzed by using binary stepwise logistic regression. In Study II, spouses’ PTG and its associated factors were explored. Data were collected through 312 questionnaires and analyzed by using multiple regression analysis. Study III explored the actor effects and partner effects of perceived social support on PTG among couples where the woman had been diagnosed with GC. Data were collected with 126 couples using questionnaires and analyzed by using Structural Equation Modeling. Study IV described the perceived professional benefits and explored the association between perceived professional benefits, sense of coherence, and coping strategies in RNs caring for women diagnosed with GC. Data were collected with 250 RNs using questionnaires and analyzed by using multiple regression analysis.The results indicate that women’s self-disclosure was positively associated with their PTG. Confrontation coping strategies, avoidance coping strategies, problem-focused coping strategies (e.g., active coping, instrumental support, and planning), and dysfunctional coping (e.g., denial, behavioral disengagement, self-distraction, and venting) were positively associated with perceived growth. Perceived social support was positively associated with PTG in both women diagnosed with GC and their spouses. Spouses’ perceived social support was positively associated with women’s perceived social support and women’s PTG. In addition, sense of coherence was positively associated with RNs’ perceived professional benefits.Based on the findings from this thesis, it is concluded that RNs need to encourage these women and their spouses to communicate their feelings, concerns, and supportive care needs, with other family members and loved ones. RNs also needs to pay more attention to the spouses’ supportive care needs, so that they are able to better support these women. It was shown that integrating effective coping strategies into existing cancer care practice may help couples to cope with the challenges related to GC. Furthermore, RNs should consider women and their spouses as a whole unit to provide effective care, and to help couples as a unit to re-evaluate their understanding of what really matters in their life. In addition, there is a need to help RNs to promote the nurse–patient relationship and a sense of belonging to the work team in their nursing practice.
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| 3. |
- Andersson, Christin, et al.
(författare)
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In vivo and in vitro lipidation of recombinant immunogens for direct iscom incorporation
- 2001
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Ingår i: Journal of Immunological Methods. - 0022-1759. ; 255:1-2, s. 135-148
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Tidskriftsartikel (refereegranskat)abstract
- We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic tags to improve their capacity to be incorporated into an adjuvant formulation (J. Immunol. Methods 222 (1999) 171; 238 (2000) 181). Here, we have explored the possibility to use in vivo or in vitro lipidation of recombinant immunogens as means to achieve iscom incorporation through hydrophobic interaction. For the in vivo lipidation strategy, a general expression vector was constructed encoding a composite tag consisting of a sequence (lpp) of the major lipoprotein of E. coli, fused to a dual affinity fusion tag to allow efficient recovery by affinity chromatography. Upon expression in E. coli, fatty acids would be linked to the produced gene products. To achieve in vitro lipidation, the target immunogen would be expressed in frame with an N-terminal His6-ABP affinity tag, in which the hexahistidyl tag was utilized to obtain lipidation via a Cu2+-chelating lipid. A 238 amino acid segment ΔSAG1, from the central region of the major surface antigen SAG1 of Toxoplasma gondii, served as model immunogen in this study. The two generated fusion proteins, lpp-His6-ABP-ΔSAG1 and His6-ABP-ΔSAG1, both expressed at high levels (approximately 5 and 100 mg/l, respectively), could be recovered to high purity by ABP-mediated affinity chromatography, and were evaluated in iscom-incorporation experiments. The His6-ABP-ΔSAG1 fusion protein was associated to iscom matrix with pre-incorporated chelating lipid. Both fusion proteins were found in the iscom fractions after analytical ultracentrifugation in a sucrose gradient, indicating successful iscom incorporation/association. Iscom formation was further supported by electron microscopy analysis. In addition, these iscom preparations were demonstrated to induce high-titer antigen-specific antibody responses upon immunization of mice. For this particular target immunogen, ΔSAG1, the induced antibodies demonstrated poor reactivity to the native antigen, although slightly better for the preparation employing the in vitro lipidation strategy, indicating that ΔSAG1 was suboptimally folded or presented. Nevertheless, we believe that the presented strategies offer convenient alternative ways to achieve efficient adjuvant incorporation for recombinant immunogens.
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| 4. |
- Elmlund, Louise
(författare)
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QCM-based sensing using biological and biomimetic interfaces
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The objective of this thesis was to explore novel approaches for studying molecular recognition at biological and biomimetic surfaces using the quartz crystal microbalance (QCM) biosensor technique. The first two papers focused on the synthesis and study of biotin selective polymer films prepared using the molecularly imprinted polymer (MIP) technique. Control over polymer structure is of importance for sensor reproducibility and sensitivity, and was addressed in Paper I where a simple strategy for fabricating uniform thin biotin imprinted polymer films was employed. In Paper II the binding of biotin moieties to thin (3-5 nm) biomimetic polymer films was examined and consequences for sensor performance discussed. The potential for using QCM as a tool for assessing the binding of small peptides derived from phage display screening was presented Paper III. Here, screening of a phage peptide library against immobilized adenine resulted in candidate peptides that were studied using this technique. In Paper IV a whole cell-based biosensor was developed for studying interactions with cell membrane-incorporated targets. Epithelial cancer cells, SKOV3, were attached to QCM sensor chips and the binding of the monoclonal antibody HerceptinTM was studied. This approach demonstrates the potential of using QCM to study binding to membrane-incorporated targets, an alternative to assays based upon immobilized receptor structures lacking their natural context.
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| 5. |
- Gamble, Carrol, et al.
(författare)
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Timing of Primary Surgery for Cleft Palate.
- 2023
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Ingår i: The New England journal of medicine. - : Massachusetts Medical Society. - 1533-4406 .- 0028-4793. ; 389:9, s. 795-807
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Tidskriftsartikel (refereegranskat)abstract
- Among infants with isolated cleft palate, whether primary surgery at 6 months of age is more beneficial than surgery at 12 months of age with respect to speech outcomes, hearing outcomes, dentofacial development, and safety is unknown.We randomly assigned infants with nonsyndromic isolated cleft palate, in a 1:1 ratio, to undergo standardized primary surgery at 6 months of age (6-month group) or at 12 months of age (12-month group) for closure of the cleft. Standardized assessments of quality-checked video and audio recordings at 1, 3, and 5 years of age were performed independently by speech and language therapists who were unaware of the trial-group assignments. The primary outcome was velopharyngeal insufficiency at 5 years of age, defined as a velopharyngeal composite summary score of at least 4 (scores range from 0 to 6, with higher scores indicating greater severity). Secondary outcomes included speech development, postoperative complications, hearing sensitivity, dentofacial development, and growth.We randomly assigned 558 infants at 23 centers across Europe and South America to undergo surgery at 6 months of age (281 infants) or at 12 months of age (277 infants). Speech recordings from 235 infants (83.6%) in the 6-month group and 226 (81.6%) in the 12-month group were analyzable. Insufficient velopharyngeal function at 5 years of age was observed in 21 of 235 infants (8.9%) in the 6-month group as compared with 34 of 226 (15.0%) in the 12-month group (risk ratio, 0.59; 95% confidence interval, 0.36 to 0.99; P=0.04). Postoperative complications were infrequent and similar in the 6-month and 12-month groups. Four serious adverse events were reported (three in the 6-month group and one in the 12-month group) and had resolved at follow-up.Medically fit infants who underwent primary surgery for isolated cleft palate in adequately resourced settings at 6 months of age were less likely to have velopharyngeal insufficiency at the age of 5 years than those who had surgery at 12 months of age. (Funded by the National Institute of Dental and Craniofacial Research; TOPS ClinicalTrials.gov number, NCT00993551.).
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| 6. |
- Herrmann, Björn, et al.
(författare)
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Chlamydia trachomatis testing : a national evaluation of internet based self-sampling in sweden
- 2019
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 95, s. A72-A72
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background Chlamydia trachomatis (CT) testing in Sweden is free of charge and now exceeds 600,000 annual tests in a population of 10 million. These tests include internet-based self-sampling tests, a service that gradually has been implemented as a part of routine diagnostics in all 21 counties. To our knowledge Sweden is the country with the highest coverage of internet based self-sampling for CT. This study evaluates the diagnostic outcome for self-sampling.Methods Requests for both self-sampling at home and clinic based sampling for CT-testing were sent to the laboratories in 18 of 21 counties. All 18 counties provided data on self-sampling in 2017 and 12 counties (representing 80% of the population) provided data on both self-collected samples at home and clinic based testing for the years 2013 to 2017.Results The proportion of self-sampling increased from 12.9% in 2013 to 17.8% in 2016 when compared to national chlamydia test figures. Between 23% and 26% of delivered test kits were never sent back for analysis during 2013–2017. In analysis of 12 counties self-sampling increased by 110% between 2013 (n=32,993) and 2017 (n=69,181) for women, compared to 67% for men (2013: n=21,008; 2017: n=35,091). Test volumes for clinic based sampling was fairly constant for both sexes (women 2013 n=245,274; 2017 n=243,338; men 2013 n=97,519; 2017 n=110,617). The proportion of men was 36% for self-sampling compared to 30% (p<0,00001) for clinic based sampling, and the positivity rate decreased for both groups from 2013 to 2017 (7,8% to 7,1% (p<0,01)) vs 9.1% to 7.0% (p<0,0001)). Corresponding figures for women went from 5.3% to 4.6% (p<0,0001)and from 4.9% to 4.1% (p<0,0001).Conclusion Self-sampling has increased significantly in recent years, especially among women.The positivity rate is similar in self-collected and clinic collected samples.Self-sampling reaches men more than clinic based testing, but not as much as expected.Disclosure No significant relationships.
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| 7. |
- Hesselman, Susanne, 1973-, et al.
(författare)
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Time matters—a Swedish cohort study of labor duration and risk of uterine rupture
- 2021
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Ingår i: Acta Obstetricia et Gynecologica Scandinavica. - : John Wiley & Sons. - 0001-6349 .- 1600-0412. ; 100:10, s. 1902-1909
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionUterine rupture is an obstetric emergency associated with maternal and neonatal morbidity. The main risk factor is a prior cesarean section, with rupture occurring in subsequent labor. The aim of this study was to assess the risk of uterine rupture by labor duration and labor management.Material and methodsThis is a Swedish register-based cohort study of women who underwent labor in 2013–2018 after a primary cesarean section (n = 20 046). Duration of labor was the main exposure, calculated from onset of regular labor contractions and birth; both timepoints were retrieved from electronic medical records for 12 583 labors, 63% of the study population. Uterine rupture was calculated as events per 1000 births at different timepoints during labor. Risk estimates for uterine rupture by labor duration, induction of labor, use of oxytocin and epidural analgesia were calculated using Poisson regression, adjusted for maternal and birth characteristics. Estimates were presented as adjusted rate ratios (ARR) with 95% confidence intervals (CI).ResultsThe prevalence of uterine rupture was 1.4% (282/20 046 deliveries). Labor duration was 9.88 hours (95% CI 8.93–10.83) for women with uterine rupture, 8.20 hours (95% CI 8.10–8.31) for women with vaginal delivery, and 10.71 hours (95% CI 10.46–10.97) for women with cesarean section without uterine rupture. Few women (1.0/1000) experienced uterine rupture during the first 3 hours of labor. Uterine rupture occurred in 15.6/1000 births with labor duration over 12 hours. The highest risk for uterine rupture per hour compared with vaginal delivery was observed at 6 hours (ARR 1.20, 95% CI 1.11–1.30). Induction of labor was associated with uterine rupture (ARR 1.54, 95% CI 1.19–1.99), with a particular high risk seen in those induced with prostaglandins and no risk observed with cervical catheter (ARR 1.19, 95% CI 0.83–1.71). Labor augmentation with oxytocin (ARR 1.60, 95% CI 1.25–2.05) and epidural analgesia (ARR 1.63, 95% CI 1.27–2.10) were also associated with uterine rupture.ConclusionsLabor duration is an independent factor for uterine rupture among women attempting vaginal delivery after cesarean section. Medical induction and augmentation of labor increase the risk, regardless of maternal and birth characteristics.
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| 8. |
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| 9. |
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| 10. |
- Lindholm, L, et al.
(författare)
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Genetic re-targeting of adenovirus using a hyperstable scFv domain and an affibody (R) molecule against Her2/neu
- 2004
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Ingår i: Molecular Therapy. - : Elsevier BV. - 1525-0016 .- 1525-0024. ; 9, s. S250-S250
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Tidskriftsartikel (refereegranskat)abstract
- One important goal in gene therapy is to develop adenovirus (Ad) vectors that are genetically de-targeted as well as re-targeted. Genetic re-targeting of Ad using complex cell-binding ligands has previously not been possible. We have previously demonstrated that ligands for genetic re-targeting of adenoviruses must be able to fold correctly in the cytoplasm of virus producing cells, a milieu that is not conducive to the formation of disulphide bonds. Here, we describe functional Ad5 viruses with fibers and pIX capsid proteins genetically modified to contain two types of complex ligands. One is affibody® molecules, corresponding to small (6 kDa) binding proteins developed by combinatorial protein engineering using a single three-helix bundle staphylococcal protein A domain. The other type is hyperstable antibody scFv domains. The affibody molecule used here (ZH2N) is directed against Her2/neu. Recombinant viruses were constructed with ZH2N in three different positions: (i) at the C-terminus of shaft repeat 7 of de-knobbed fibers; (ii) at the C-terminus of pIX; and (iii) in the HI-loop of the fiber knob. Each of the viruses exhibited a characteristic phenotype regarding fiber content, growth and ability to infect Her2/neu expressing cells. In order to test the potentials of scFv liganded Ad vectors, a hyperstable antibody scFv against b-galactosidase was genetically incorporated into knobless fibers, in tandem with a mutated protein A domain reactive with IgG1 Fc that targeted the virus to Fc-expressing 293 cells. These fibers could be rescued into viable virions that retained the original antigen binding specificity of the scFv, demonstrating the basic potential of hyperstable scFvs for genetic re-targeting of Ad. Quite unexpectedly, the fiber content of Ad with knobless, scFv containing fibers was close to normal in contrast to other Ad with knobless fibers that generally has a much reduced fiber content. The hyperstable scFv was further fused to the C-terminus of the capsid protein pIX. The recombinant molecules could be rescued into viable viruses with wt fibers. The scFv retained its binding-specificity on the recombinant virions. The results demonstrate that, contrary to current beliefs, it is possible to construct Ad that genetically incorporates functional scFvs and other complex ligands into the virus fiber and pIX. The feasibility is demonstrated by the creation of different viruses that are re-targeted to Her2/neu. These viruses are currently in pre-clinical development.
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| 11. |
- Ljungman, Lisa, 1981-, et al.
(författare)
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Psychometric properties of the Swedish version of the Parenting Concerns Questionnaire in parents with cancer
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63:1, s. 592-599
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: Parenting concerns can be a major source of distress for patients with cancer who are parents of dependent children; however, these are often not addressed in health care. The Parenting Concerns Questionnaire (PCQ) is an instrument designed to assess parents' worries about the impact of cancer on their children and their ability to parent during this time. The Swedish version of the PCQ has, however, not been evaluated. This study therefore aimed to examine the psychometric properties of the PCQ in a sample of Swedish parents with cancer.Material and methods: A sample of 336 patients with cancer having dependent children (<= 18 years) were included in a cross-sectional web-based survey. Participants completed questionnaires assessing parenting concerns, depression, anxiety, and stress symptoms (DASS); self-efficacy, family functioning (FAD-GF); and sociodemographic and clinical characteristics. Descriptive analyses, as well as reliability and validity analyses, were conducted followed by a confirmatory factor analysis of the factor structure proposed by the authors of the original version of the PCQ.Results: The majority were mothers (94.9%) with breast cancer (66.4%) aged 40-50 years (59.5%). The results showed evidence for convergent, criterion, and known group's validity, but the original three-factor structure of the PCQ was not fully supported by confirmatory factor analysis.Interpretation: Evaluating parenting concerns may be an important step towards identifying patients who could benefit from targeted psychosocial interventions. However, the PCQ may require some further refinement to fully capture the breadth of parenting concerns in parents with cancer in different settings.
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| 12. |
- Magnusson, Maria K, 1972, et al.
(författare)
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Adenovirus 5 vector genetically re-targeted by an Affibody molecule with specificity for tumor antigen HER2/neu.
- 2007
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Ingår i: Cancer gene therapy. - : Springer Science and Business Media LLC. - 0929-1903 .- 1476-5500. ; 14:5, s. 468-79
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Tidskriftsartikel (refereegranskat)abstract
- In order to use adenovirus (Ad) type 5 (Ad5) for cancer gene therapy, Ad needs to be de-targeted from its native receptors and re-targeted to a tumor antigen. A limiting factor for this has been to find a ligand that (i) binds a relevant target, (ii) is able to fold correctly in the reducing environment of the cytoplasm and (iii) when incorporated at an optimal position on the virion results in a virus with a low physical particle to plaque-forming units ratio to diminish the viral load to be administered to a future patient. Here, we present a solution to these problems by producing a genetically re-targeted Ad with a tandem repeat of the HER2/neu reactive Affibody molecule (ZH) in the HI-loop of a Coxsackie B virus and Ad receptor (CAR) binding ablated fiber genetically modified to contain sequences for flexible linkers between the ZH and the knob sequences. ZH is an Affibody molecule specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) that is overexpressed in inter alia breast and ovarian carcinomas. The virus presented here exhibits near wild-type growth characteristics, infects cells via HER2/neu instead of CAR and represents an important step toward the development of genetically re-targeted adenoviruses with clinical relevance.
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| 13. |
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| 14. |
- Melander-Wikman, Anita, et al.
(författare)
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Methodology for empowering elderly persons in home care by means of ICT
- 2006
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Ingår i: Telemedicin and eHealth Beyond Tomorrow. ; , s. 83-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- If future demands on health and home care are to be met effectively, implementing information and communication technology (ICT) is acknowledged as a necessity. New (mobile) ICT may also be seen as a tool for empowering elderly people. Enabling the right to self-determination among the elderly will also change professionals'ways of thinking, and thus the basis of their involvement. In the e-Home Health Care @ North Calotte project (eHHC, 2003-2005) a set of guidelines was developed for a methodology for empowennent when implementing mobile ICT into home healthcare. This project coordinated field trials in four municipalities in northern Finland, Norway and Sweden. The Swedish trial used a Participatory Action Research approach (PAR) and included Future Workshops, focus-group interviews, reflective interviews and observations. The aim of this study is to present the working process and the methods used when creating guidelines for a methodology for empowerment. The dimensions of empowennent are discussed, together with results from the Swedish trial in the eHHC project. The experiences from this trial show that to ensure the empowerment process when developing ICT in home care, close cooperation with clients, relatives and professionals is needed.
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| 15. |
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| 16. |
- Melander-Wikman, Anita, et al.
(författare)
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MobiHealth projektet - mobil teknik
- 2003
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Ingår i: Abstractbok för sjukgymnasdagarna 2003. - Stockholm : Legitimerade sjukgymnasters riksförbund. ; , s. 49-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 17. |
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| 18. |
- Melander-Wikman, Anita, et al.
(författare)
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Positionering av äldre : "storebror ser dig"
- 2005
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Ingår i: Abstractbok för sjukgymnastdagarna 2005. - Stockholm : Legitimerade sjukgymnasters riksförbund. ; , s. 30-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 19. |
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| 20. |
- Melander-Wikman, Anita, et al.
(författare)
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Reflections on an appreciative approach to empowering elderly people in home healthcare
- 2006
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Ingår i: Reflective Practice. - : Taylor & Francis. - 1462-3943 .- 1470-1103. ; 7:4, s. 423-443
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Tidskriftsartikel (refereegranskat)abstract
- This is a reflective account of aspects of our collective concern about developing and sustaining ways that might enable elderly people to feel more empowered to exercise their right of self-determination. This work has been undertaken in the context of home healthcare in northern Sweden. In this paper we put three espoused values 'under pressure' from client, professional (homecare staff) and research perspectives. We also explore three aspects of the pictorial landscape of homecare (see Figure 1). They are the notions of client participation, empowerment and ICT. The living data for this paper is drawn from two days of workshop activities with 35 homecare staff working in the municipality of Lule, Sweden. The workshop was one outcome of the e-Home Health Care @ North Calotte (eHHC) Project of 2003-2005. We conclude with some collective reflections about: (a) the practice of participation (dialogue) and an intention of it (empowerment) in the context of clients accelerating service change; (b) how to reframe traditional views of the relationships between research and practice and, as a consequence, open up new possibilities for understanding how elderly people's lived experiences can be a positive force for service improvement; and (c) the use of storyboards as an appreciative approach to enable frontline staff to reflect on their work, share and learn together
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| 21. |
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| 22. |
- Melander-Wikman, Anita, et al.
(författare)
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The lighthouse alarm and locator trial : a pilot study
- 2007
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Ingår i: Technology and Health Care. - : EBSCO Industries, Inc. - 0928-7329 .- 1878-7401. ; 15:3, s. 203-212
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Tidskriftsartikel (refereegranskat)abstract
- An important factor for health is the possibility to be active and mobile. To make this possible different kind of support are needed. Integrating geographical information systems technology and user experiences is important in the development of more user-friendly positioning devices. The Lighthouse Alarm and Locator trial aimed to test a new mobile alarm system with additional functionality such as positioning and monitoring of vital signs which can be used regardless of location (in hospital, at home). The system was tested by elderly persons from a pensioner organisation and home care personnel answered up on the alarms. After the tests qualitative interviews were performed with the two groups. The results showed that their experiences of the new mobile alarm system could be described in three main categories: to be supervised, to feel safe and to be mobile. These categories formed a theme: Positioning - an ethical dilemma. The clients' mobility was perceived to increase. The personnel did not think that positioning was ethical but the clients (elderly) did.
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| 23. |
- Melander-Wikman, Anita, et al.
(författare)
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The MobiHealth usability evaluation questionnaire
- 2005
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Ingår i: eHealth International. - 1476-3591. ; 2:1, s. 9-14
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Tidskriftsartikel (refereegranskat)abstract
- There is a need for high quality evaluation instruments when testing new mobile devices and services. The aim of this study was to describe the development of the MobiHealth Usability Evaluation Questionnaire. It was developed in a step-wise consensus process with close interaction between researchers, technology developers and end-users. The questionnaire ten dimensions: functionality, user interface, effectiveness, efficiency, satisfaction, safety, functional and aspirational needs, mastery and empowerment, mobility and activity, quality of life and ethical considerations. These dimensions are defined and their usage as parameters in an evaluation instrument is discussed. The conclusion is that the MobiHealth Evaluation Questionnaire can be used as a basis for method development when evaluating mobile care and rehabilitative devices, but it should be tested for reliability before actual use.
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| 24. |
- Mulvenna, Maurice, et al.
(författare)
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Towards sustainable business models from healthcare technology research
- 2010
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Ingår i: International Journal of Computers in Healthcare (IJCIH). - : InderScience Publishers. - 1755-3199 .- 1755-3202. ; 1:1, s. 20-34
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Tidskriftsartikel (refereegranskat)abstract
- As demographic ageing impacts across the world, health and welfare organisations are seeking new paradigms of care that address people's needs as well as being inherently more scalable than the incumbent processes and services. The aim of this paper is to describe the current situation in Europe with information on service provision, before signposting some possible new ways to develop sustainable business models that support care models. The paper uses a case study approach to examine the issues in the introduction of such business models, from a perspective of the translation of research proof of concepts into business services and from the perspective of developing innovations from research that address unmet or poorly considered needs of user. The paper shows how several innovative European projects are anticipating the need for service change and are designing their research outcomes to match the needs of service commissioners more fully. The conclusion discusses several different approaches before drawing together strands of the work and providing tentative recommendations on the way forward to develop new inclusive technology-enhanced services in health and social care.
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| 25. |
- Mulvenna, Maurice, et al.
(författare)
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Towards sustainable business models from technology healthcare research
- 2010
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Ingår i: International Journal of Computers in Healthcare (IJCIH). - Geneve : Inderscience Enterprises Lilmited. - 1755-3199. ; 1:1, s. 43-51
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Tidskriftsartikel (refereegranskat)abstract
- As demographic ageing impacts across the world, health and welfare organisations are seeking new paradigms of care that address people’s needs as well as being inherently more scalable than the incumbent processes and services. The aim of this paper is to describe the current situation in Europe with information on service provision, before signposting some possible new ways to develop sustainable business models that support care models. The paper uses a case study approach to examine the issues in the introduction of such business models, from a perspective of the translation of research proof of concepts into business services and from the perspective of developing innovations from research that address unmet or poorly considered needs of user. The paper shows how several innovative European projects are anticipating the need for service change and are designing their research outcomes to match the needs of service commissioners more fully. The conclusion discusses several different approaches before drawing together trands of the work and providing tentative recommendations on the way forward to develop new inclusive technology-enhanced services in health and social care.
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| 26. |
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| 27. |
- Orlova, Anna, et al.
(författare)
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Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 Affibody for single-photon imaging of HER2 expression in tumors
- 2006
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Ingår i: Journal of Nuclear Medicine. - 0161-5505 .- 1535-5667. ; 47:3, s. 512-519
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Tidskriftsartikel (refereegranskat)abstract
- In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, HiS(6)-(ZHER(2:4))(2) (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of Tc-99m might improve the availability of the labeled conjugate, and Tc(l)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare Tc-99m-labeled Hi0S(6)-(Z(HER2:4))(2) and to evaluate its targeting properties compared with the targeting properties of I-125 -4-iodobenzoate-HiS(6)-(Z(HER2:4))(2) [I-125-HiS(6)-(Z(HER2:4))(2)]- Methods: The labeling of HiS6-(Z(HER2:4))2 with Tc-99m was performed with an IsoLink kit. The specificity of Tc-99m-HiS(6)-(Z(HER2:4))(2) binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of Tc-99m-HiS(6)-(Z(HER2,4))(2) and I-125-HiS(6)-(Z(HER2:4))(2) in tumor-bearing BALB/c nulnu mice were determined. Results: The labeling yield for Tc-99m-HIS6(Z(HER2:4))(2) was similar to 60% (50 degrees C), and the radiochernical purity was greater than 97%. The conjugate was stable during storage and under histicline and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%]A/gj) of 2.6 %IA/g for Tc-99m-HiS(6)-(Z(HER2:4))(2) and 2.3 % IA/g for I-125-HiS6-(Z(HER2:4))(2) at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. Conclusion: The use of Tc(l)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-HiS(6)-(Z(HER2:4))(2) conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with Tc-99m should be investigated further.
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| 28. |
- Pinitkiatisakul, S., et al.
(författare)
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Immunisation of mice against neosporosis with recombinant NcSRS2 iscoms
- 2005
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Ingår i: Veterinary parasitology. - : Elsevier BV. - 0304-4017 .- 1873-2550. ; 129:1-2, s. 25-34
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Tidskriftsartikel (refereegranskat)abstract
- The coccidian parasite Neospora caninum is an intracellular protozoan, causing abortion in cattle in many countries around the world. In this study, the protective potential of the major N. caninum surface antigen NcSRS2, expressed in Escherichia coli and formulated into immunostimulating complexes (iscoms), was investigated in an experimental mouse model. The recombinant protein was specially designed for binding to iscoms via biotin-streptavidin interaction. Two groups of 10 BALB/c mice were immunised twice, on days 0 and 28 with iscoms containing either the recombinant NcSRS2 (NcSRS2 iscoms) or similar iscoms with NcSRS2 substituted by an unrelated recombinant malaria peptide (M5) as a control (M5 iscoms). A third group of 10 age-matched BALB/c mice served as an uninfected control group. Immunisation with recombinant NcSRS2 iscoms resulted in production of substantial antibody titres against N. caninum antigen, while the mice immunised with M5 iscoms produced only very low levels of antibodies reacting with N. caninum antigen. After challenge infection with N. caninum tachyzoites on day 69, mice immunised with NcSRS2 iscoms showed only mild and transient symptoms, whereas the group immunised with M5 iscoms showed clinical symptoms until the end of the experiment at 31 days post inoculation. A competitive PCR assay detecting Nc5-repeats was applied to evaluate the level of parasite DNA in the brain. The amount of Nc5-repeats in the group vaccinated with NcSRS2 iscoms was significantly lower than in the control group given M5 iscoms. In conclusion, it was found that the recombinant NcSRS2 iscoms induced specific antibodies to native NcSRS2 and immunity sufficient to reduce the proliferation of N. caninum in the brains of immunised mice.
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| 29. |
- Pinitkiatisakul, Sunan, et al.
(författare)
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Immunogenicity and protective effect against murine cerebral neosporosis of recombinant NcSRS2 in different iscom formulations
- 2007
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 25:18, s. 3658-3668
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Tidskriftsartikel (refereegranskat)abstract
- Recombinant NcSRS2, a major immunodominant surface antigen of the intracellular protozoan parasite Neospora caninum, was used as a model antigen to compare the immunogenicity of iscoms prepared according to three different methods. Two NcSRS2 fusion proteins were used, one that was biotinylated upon expression in Escherichia coli and linked to Ni2+-loaded iscom matrix (iscom without any protein) via a hexabistidyl (HiS(6)-tagged streptavidin fusion protein, and another that contained both a HiS(6)-tag and streptavidin (HiS(6)-SA-SRS2') and was coupled to either Ni2+-loaded or biotinylated matrix. While all three iscom preparations induced N. caninum specific antibodies at similar levels, HiS(6)-SA-SRS2' coupled to biotinylated matrix generated the strongest cellular responses measured as in vitro proliferation and production of interferon-gamma and interleukin-4 after antigen stimulation of spleen cells. However, the relationship between the levels of these cytokines as well as between IgG1 and IgG2a titres in serum induced by the three iscom preparations were similar, indicating that the balance between Th1 and Th2 responses did not differ. After challenge infection, mice immunised with His(6)-SA-SRS2' coupled to biotinylated matrix had significantly lower amounts of parasite DNA in their brains compared to the other immunised groups. Possible reasons for the performance of the different iscom formulations are discussed.
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| 30. |
- Romare Strandh, Maria, et al.
(författare)
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Parenting under pressure : a cross-sectional questionnaire study of psychological distress, parenting concerns, self-efficacy, and emotion regulation in parents with cancer
- 2024
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Ingår i: Acta Oncologica. - : Medical Journals Sweden. - 0284-186X .- 1651-226X. ; 63
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose: As many as one in four adults with cancer have children under 18 years. Balancing parenting and cancer is challenging and can be a source of psychological distress. This study aimed to examine psychological distress in parents with cancer and its associations with parenting concerns, self -efficacy, and emotion regulation.Materials and methods: This was a cross-sectional questionnaire study of 406 parents (aged 25-60 years) diagnosed with cancer within the last 5 years, with at least one dependent child (<= 18 years). Parents completed questionnaires on psychological distress (DASS-21), parenting concerns (PCQ), self -efficacy (GSE), emotion regulation (ERQ), mental and physical health, and sociodemographics. Data were analysed using multiple logistic regressions on depression (yes/no), anxiety (yes/no), and stress (yes/no).Results: Higher parenting concerns were associated with greater odds of depression (OR = 2.33, 95% CI: 1.64-3.31), anxiety (OR = 2.30, 95% CI: 1.64-3.20), and stress (OR = 3.21, 95% CI: 2.20-4.69) when adjusting for health and sociodemographic factors. Poorer self -efficacy was associated with increased odds of anxiety (OR = 0.94, 95% CI: 0.89-0.99, p < 0.05), whereas lower use of cognitive reappraisal and higher use of expressive suppression increased the odds of depression (OR = 0.76, 95% CI: 0.59-0.98 | OR = 1.46, 95% CI: 1.18-1.80).Interpretation: The findings highlight the complexity of parental well-being in relation to parenthood and cancer, stressing the need for interventions that address relevant psychological factors to improve overall mental health in this population.
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| 31. |
- Romare Strandh, Maria, et al.
(författare)
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Psychosocial interventions targeting parenting distress among parents with cancer : A systematic review and narrative synthesis of available interventions
- 2023
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Ingår i: Critical reviews in oncology/hematology. - : Elsevier. - 1040-8428 .- 1879-0461. ; 191
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Forskningsöversikt (refereegranskat)abstract
- BackgroundBalancing having cancer and parenting a major stressor, and may result in parenting distress, negatively affecting the whole family. To provide adequate support, knowledge of existing psychosocial interventions are crucial to guide future interventions. This study aimed to describe available psychosocial interventions for parents with cancer and dependent children (<18 years).MethodWe conducted a systematic review, and four databases were searched from January 2000 to March 2023.ResultsThirty studies were included, reporting on 22 psychosocial interventions for parents with cancer. They aimed to improve different aspects of parenting distress, and included psychoeducation and communication strategies. Interventions were beneficial to and acceptable among parents, but only a few had been evaluated. The study quality was, overall, assessed as moderate.ConclusionsThe results of this review highlight the diversity of available psychosocial interventions for parents with cancer and the outcomes on parenting distress, as well as methodological challenges.
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| 32. |
- Romare Strandh, Maria, et al.
(författare)
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The Complexity of Being a Parent in the Hospital and a Patient at Home : A Qualitative Study on Parenting Concerns and Challenges Among Parents With Cancer
- 2023
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Ingår i: Cancer Nursing. - 0162-220X .- 1538-9804.
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Tidskriftsartikel (refereegranskat)abstract
- Background Parents given a diagnosis of cancer must balance the demands of their illness and caregiving responsibilities. This can result in parental stress and have a negative impact on the well-being of the whole family. A greater understanding of the experiences of parents with cancer is necessary to provide adequate support.Objective The aim of this study was to explore parenting concerns and challenges among parents with cancer who were caring for dependent children younger than 18 years.Methods Semistructured interviews were carried out with 22 parents with cancer. Interviews were audio-recorded, transcribed, and analyzed using thematic analysis.Results Parental concerns and challenges affected parents in their parental role and their everyday family life. Three overarching themes described the struggles in balancing life as a parent and as a patient: navigating dual roles as a parent with cancer, impact of cancer on parenting, and impact on family life. Parents’ primary focus was on their children’s well-being, and they struggled to manage their own expectations of parenting and the demands on their role in the family.Conclusion The results highlight the complexity of being a parent with cancer while caring for dependent children. To support parents during the cancer journey, it is important to understand the consequences of their illness on their parental role and the family.Implications for Practice Supporting parents to feel secure in their parental role and providing support to them during their cancer journey should be integrated into routine cancer care, where parenting concerns and challenges are addressed.
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| 33. |
- Steffen, A.C, et al.
(författare)
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Affibody mediated tumor targeting of HER-2 expressing xenografts in mice
- 2006
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Ingår i: European Journal of Nuclear Medicine and Molecular Imaging. - : Springer Science and Business Media LLC. - 1619-7070 .- 1619-7089. ; 33:6, s. 631-638
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Targeted delivery of radionuclides for diagnostic and therapeutic applications has until recently largely been limited to receptor ligands, antibodies and antibody-derived molecules. Here, we present a new type of molecule, a 15-kDa bivalent affibody called (Z(HER2:4))(2), with potential for such applications. The (Z(HER2:4))(2) affibody showed high apparent affinity (K (D)=3 nM) towards the oncogene product HER-2 (also called p185/neu or c-erbB-2), which is often overexpressed in breast and ovarian cancers. The purpose of this study was to investigate the in vivo properties of the new targeting agent. METHODS: The biodistribution and tumour uptake of the radioiodinated (Z(HER2:4))(2) affibody was studied in nude mice carrying tumours from xenografted HER-2 overexpressing SKOV-3 cells. RESULTS: The radioiodinated (Z(HER2:4))(2) affibody was primarily excreted through the kidneys, and significant amounts of radioactivity were specifically targeted to the tumours. The blood-borne radioactivity was, at all times, mainly in the macromolecular fraction. A tumour-to-blood ratio of about 10:1 was obtained 8 h post injection, and the tumours could be easily visualised with a gamma camera at this time point. CONCLUSION: The results indicate that the (Z(HER2:4))(2) affibody is an interesting candidate for applications in nuclear medicine, such as radionuclide-based tumour imaging and therapy.
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| 34. |
- Steffen, Ann-Charlott, et al.
(författare)
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In vitro characterization of a bivalent anti-HER-2 affibody with potential for radionuclide-based diagnostics
- 2005
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Ingår i: Cancer Biotherapy and Radiopharmaceuticals. - : Mary Ann Liebert Inc. - 1084-9785 .- 1557-8852. ; 20:3, s. 239-248
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Tidskriftsartikel (refereegranskat)abstract
- The 185 kDa transmembrane glycoprotein human epidermal growth factor receptor 2 (HER-2) (p185/neu, c-ErbB-2) is overexpressed in breast and ovarian cancers. Overexpression in breast cancer correlates with poor patient prognosis, and visualization of HER-2 expression might provide valuable diagnostic information influencing patient management. We have previously described the generation of a new type of affinity ligand, a 58-amino-acid affibody (Z(HER2:4)) with specific binding to HER-2. In order to benefit from avidity effects, we have created a bivalent form of the affibody ligand, (Z(HER2:4))2. The monovalent and bivalent ligands were compared in various assays. The new bivalent affibody has a molecular weight of 15.6 kDa and an apparent affinity (K(D)) against HER-2 of 3 nM. After radioiodination, using the linker molecule N-succinimidyl p-(trimethylstannyl) benzoate (SPMB), in vitro binding assays showed specific binding to HER-2 overexpressing cells. Internalization of 125I was shown after delivery with both the monovalent and the bivalent affibody. The cellular retention of 125I was longer after delivery with the bivalent affibody when compared to delivery with the monovalent affibody. With approximately the same affinity as the monoclonal antibody trastuzumab (Herceptin) but only one tenth of the size, this new bivalent molecule is a promising candidate for radionuclide-based detection of HER-2 expression in tumors. 125I was used in this study as a surrogate marker for the diagnostically relevant radioisotopes 123I for single photon emission computed tomography (SPECT)/gamma-camera imaging and 124I for positron emission tomography (PET).
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| 35. |
- Söderqvist, Joakim, et al.
(författare)
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Internet-based self-sampling for Chlamydia trachomatis testing : a national evaluation in Sweden
- 2020
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Ingår i: Sexually Transmitted Infections. - : BMJ Publishing Group Ltd. - 1368-4973 .- 1472-3263. ; 96:3, s. 160-165
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Tidskriftsartikel (refereegranskat)abstract
- Objective Internet-based testing for Chlamydia trachomatis (CT) with self-sampling at home has gradually been implemented in Sweden since 2006 as a free-of-charge service within the public healthcare system. This study evaluated the national diagnostic outcome of this service. Methods Requests for data on both self-sampling at home and clinic-based sampling for CT testing were sent to the laboratories in 18 of 21 counties. Four laboratories were also asked to provide data on testing patterns at the individual level for the years 2013-2017. Results The proportion of self-sampling increased gradually from 2013, comprising 22.0% of all CT tests in Sweden in 2017. In an analysis of 14 counties (representing 83% of the population), self-sampling increased by 115% between 2013 and 2017 for women, compared with 71% for men, while test volumes for clinic-based sampling were fairly constant for both sexes (1.8% increase for women, 15% increase for men). In 2017 self-sampling accounted for 20.3% of all detected CT cases, and the detection rate was higher than, but similar to, clinic-based testing (5.5% vs 5.1%). The proportion of self-sampling men was also higher, but similar (33.7% vs 30.8%). Analysis of individual testing patterns in four counties over 5 years showed a higher proportion of men using self-sampling only (67%, n=10 533) compared with women (40%, n=8885). Conclusions Self-sampling has increased substantially in recent years, especially among women. This service is at least as beneficial as clinic-based screening for detection of CT, and self-sampling reaches men more than clinic-based testing.
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| 36. |
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| 37. |
- Wikman, Maria, et al.
(författare)
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Achieving directed immunostimulating complex incorporation
- 2006
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Ingår i: Expert Review of Vaccines. - : Informa UK Limited. - 1476-0584 .- 1744-8395. ; 5:3, s. 395-403
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Forskningsöversikt (refereegranskat)abstract
- In recent years, several studies have been reported with the common aim of generating general expression systems for straightforward production and subsequent coupling of expressed antigens to an adjuvant system. Here, we describe a series of such efforts with a common theme of using gene fusion technology for association of recombinant antigens to immunostimulating complexes (iscoms). In the early stages of vaccine development, uniform antigen preparations are crucial to allow the comparison of immune responses to different antigens, or even subdomains thereof, and we believe that the described systems constitute an important development in this context.
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| 38. |
- Wikman, Maria, et al.
(författare)
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Applying biotin-streptavidin binding for iscom (immunostimulating complex) association of recombinant immunogens
- 2005
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Ingår i: Biotechnology and applied biochemistry. - 0885-4513 .- 1470-8744. ; 41, s. 163-174
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Tidskriftsartikel (refereegranskat)abstract
- We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptide or lipid tags to improve their capacity to be incorporated into an adjuvant formulation. In the present study, we have explored the strong interaction between biotin and SA (streptavidin) (K-D approximate to 10(-15) M) to couple recombinant immunogens to iscoms (immunostimulating complexes). Two different concepts were evaluated. In the first concept, a His(6)-tagged SA fusion protein (His(6)-SA) was bound to Ni2+-loaded iscom matrix (iscom without associated protein), and biotinylated immunogens were thereafter associated with the SA-coated iscoms. The immunogens were either biotinylated in vivo on E. coli expression or double biotinylated in vivo and in vitro. In the second concept, the recombinant immunogens were expressed as SA fusion proteins, which were directly bound to a biotinylated iscom matrix. A 53-amino-acid malaria peptide (M), derived from the central repeat region of the Plasmodium faiciparum blood-stage antigen Pf155/RESA, and a 232-amino-acid segment (SRS2') from the central region (from Pro-97 to Lys-328) of the major surface antigen NcSRS2 of the protozoan parasite Neospora caninum, served as model immunogens in the present study. All fusion proteins generated were found to be efficiently expressed and could be recovered to high purity using affinity chromatography. The association between the different immunogen-containing fusion proteins and the corresponding iscom matrix was demonstrated by analytical ultracentrifugation in a sucrose density gradient. However, some fusion proteins were, to a certain extent, also found to associate unspecifically with a regular iscom matrix. Furthermore, selected iscom fractions were demonstrated to induce high-titre antigen-specific antibody responses on immunization of mice. For the particular target immunogen SRS2', the induced antibodies demonstrated reactivity to the native antigen NcSRS2. We believe that the presented concepts offer convenient methods to achieve efficient adjuvant association of recombinant immunogens, and the advantages and disadvantages of the two concepts are discussed.
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| 39. |
- Wikman, Maria, et al.
(författare)
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General strategies for efficient adjuvant incorporation of recombinant subunit immunogens
- 2005
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Ingår i: Vaccine. - : Elsevier BV. - 0264-410X .- 1873-2518. ; 23:17-18, s. 2331-2335
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Tidskriftsartikel (refereegranskat)abstract
- We have previously reported strategies for Escherichia coli production of recombinant immunogens fused to hydrophobic peptides or lipid tags to improve their capacity to be incorporated into an adjuvant formulation, e.g., immunostimulating complexes (iscoms). Recently, we also explored the strong interaction between biotin and streptavidin to achieve iscom association of recombinant immunogens. Plasmodium falciparum, Toxoplasma gondii and Neospora caninum antigens have served as model immunogens in the different studies. Generated fusion proteins have been found to be successfully incorporated into iscoms and high-titer antigen-specific antibody responses have been obtained upon immunization of mice. We believe that the different concepts presented, utilizing either hydrophobic peptide or lipid tags, or the recently explored biotin-streptavidin principle, offer convenient methods to achieve efficient adjuvant incorporation of recombinant immunogens.
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| 40. |
- Wikman, Maria
(författare)
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Rational and combinatorial protein engineering for vaccine delivery and drug targeting
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis describes recombinant proteins that have been generated by rational and combinatorial protein engineering strategies for use in subunit vaccine delivery and tumor targeting.In a first series of studies, recombinant methods for incorporating immunogens into an adjuvant formulation, e.g. immunostimulating complexes (iscoms), were evaluated. Protein immunogens, which are not typically immunogenic in themselves, are normally administered with an adjuvant to improve their immunogenicity. To accomplish iscom incorporation of a Toxoplasma gondii surface antigen through hydrophobic interaction, lipids were added either in vivo via E. coli expression, or in vitro via interaction of an introduced hexahistidyl (His6) peptide and a chelating lipid. The possibility of exploiting the strong interaction between biotin and streptavidin was also explored, in order to couple a Neospora caninum surface antigen to iscom matrix, i.e. iscom particles without any antigen. Subsequent analyses confirmed that the immunogens were successfully incorporated into iscoms by the investigated strategies. In addition, immunization of mice with the recombinant Neospora antigen NcSRS2, associated with iscoms through the biotin-streptavidin interaction, induced specific antibodies to native NcSRS2 and reduced clinical symptoms following challenge infection. The systems described in this thesis might offer convenient and efficient methods for incorporating recombinant immunogens into adjuvant formulations that might be considered for the generation of future recombinant subunit vaccines.In a second series of studies, Affibody® (affibody) ligands directed to the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu), which is known to be overexpressed in ∼ 20-30% of breast cancers, were isolated by phage display in vitro selection from a combinatorial protein library based on the 58 amino acid residue staphylococcal protein A-derived Z domain. Biosensor analyses demonstrated that one of the variants from the phage selection, denoted His6-ZHER2/neu:4, selectively bound with nanomolar affinity (KD ≈ 50 nM) to the extracellular domain of HER2/neu (HER2-ECD) at a different site than the monoclonal antibody trastuzumab. In order to exploit avidity effects, a bivalent affibody ligand was constructed by head-to-tail dimerization, resulting in a 15.6 kDa affibody ligand, termed His6-(ZHER2/neu:4)2, that was shown to have an improved apparent affinity to HER2-ECD (KD ≈ 3 nM) compared to the monovalent affibody. Moreover, radiolabeled monovalent and bivalent affibody ligands showed specific binding in vitro to native HER2/neu molecules expressed in human cancer cells. Biodistribution studies in mice carrying SKOV-3 xenografted tumors revealed that significant amounts of radioactivity were specifically targeted to the tumors in vivo, and the tumors could easily be visualized with a gamma camera. These results suggest that affibody ligands would be interesting candidates for specific tumor targeting in clinical applications, such as in vivo imaging and radiotherapy.
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| 41. |
- Wikman, Maria, et al.
(författare)
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Selection and characterization of an HIV-1 gp120-binding affibody ligand
- 2006
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Ingår i: Biotechnology and applied biochemistry. - : Wiley. - 0885-4513 .- 1470-8744. ; 45, s. 93-105
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Tidskriftsartikel (refereegranskat)abstract
- To evaluate the possibility of generating novel proteins binding to highly glycosylated viral proteins, affibody ligands were selected by bactericiphage display technology to the HIV-1 envelope glycoprotein gp120 (glycoprotein 120), from a combinatorial protein library based on the 58-amino-acid-residue staphylococcal Protein A domain. The predominant variant from the bacteriophage selection was produced in Escherichia coli and characterized by biosenscir analyses. Both univalent and bivalent affibody molecules were shown to bind selectively to the gp120 target molecule in a biosensor analysis. The dissociation equilibrium constants (K.) were determined to be approx. 100 nM for the univalent affibody and 10 nM for the bivalent affibody, confirming the stronger gp120 binding of the bivalent affibody ligand. The affibody constructs were further introduced into the AdS (adenovirus type 5) fibre gene, and the recombinant fibres were shown to bind selectively to gp 120 in a biosensor analysis and to gp160 transiently expressed in African-green-monkey (Cercopithecus aethiops) kidney cells. Neither the affibody ligand nor the AdS fibres showed any virus neutralization activity, suggesting that the affibody bound to a non-neutralizing site on gp 120. To investigate the binding site for the affibody ligand on gp120, CD4 (cluster of differentiation 4) and a panel of mAbs (monoclonal antibodies) known to bind to gp 120 were allowed to compete with the affibody ligand in a biosensor study. Two mAbs, 670-30D and 697-30D, were found to compete with gp120 for overlapping binding sites. Although neutralization effects were not achieved in this initial investigation, the successful selection of a gp120-binding affibody ligand indicates that future affibody-based strategies might evolve to complement antibody-based efforts for HIV-I therapy. Strategies for directed selection of affibody ligands binding to neutralizing epitopes and the potential of using adenovirus for gene-therapy-mediated efforts are discussed.
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| 42. |
- Wikman, Maria, et al.
(författare)
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Selection and characterization of HER2/neu-binding affibody ligands
- 2004
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Ingår i: Protein Engineering Design & Selection. - : Oxford University Press (OUP). - 1741-0126 .- 1741-0134. ; 17:5, s. 455-462
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Tidskriftsartikel (refereegranskat)abstract
- Affibody (affibody) ligands that are specific for the extracellular domain of human epidermal growth factor receptor 2 (HER2/neu) have been selected by phage display technology from a combinatorial protein library based on the 58 amino acid residue staphylococcal protein A-derived Z domain. The predominant variants from the phage selection were produced in Escherichia coli, purified by affinity chromatography, and characterized by biosensor analyses. Two affibody variants were shown to selectively bind to the extracellular domain of HER2/neu (HER2-ECD), but not to control proteins. One of the variants, denoted His6-ZHER2/neu:4, was demonstrated to bind with nanomolar affinity (approximately 50 nM) to the HER2-ECD molecule at a different site than the monoclonal antibody trastuzumab. Furthermore, radiolabeled His6-ZHER2/neu:4 affibody showed specific binding to native HER2/neu, overexpressed on the SKBR-3 tumor cell line. Such affibody ligands might be considered in tumor targeting applications for radionuclide diagnostics and therapy of adenocarcinomas such as breast and ovarian cancers.
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