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- Ekerljung, Lina, 1980-
(författare)
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EGFR- and HER2-Binding Affibody Molecules : Cellular studies of monomeric, dimeric and bispecific ligands
- 2011
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Abnormal expression and signaling of the ErbB receptors is associated with the development and progression of several forms of cancer. In this thesis, new ErbB-targeting affibody molecules are evaluated regarding their cellular effects in vitro. Since ligand binding to an ErbB receptor might have an impact on the cell it is important to be aware of these effects as they may have consequences for the continued growth of the tumor when used in vivo. The affibody molecules are intended for tumor targeting with the prospect of clinical use in imaging or therapy. Three types of affibody molecules were studied, HER2-binding, EGFR-binding and bispecific binders that target both EGFR and HER2. The HER2-targeting (ZHER2:342)2 showed promising characteristics. It sensitized SKBR-3 cells to irradiation and decreased cell growth to the same extent as the clinically approved antibody Herceptin. The monomeric version, ZHER2:342, did not induce any large effects on intracellular signaling or biological outcome. This makes (ZHER2:342)2 interesting for therapy purposes, while ZHER2:342 may be better suited for imaging. The bispecific affibody molecules were all able to simultaneously bind to both EGFR and HER2, but none of the six constructs resulted in any large effects on cellular outcome. Interestingly, all three monovalent binders are more functional when positioned at the N-terminal part of the construct and the (S4G)3 linker renders higher affinity of the bispecific binders compared to (G4S)3. Tumors that co-express several ErbB receptors are often more aggressive and associated with a worse prognosis, suggesting that the total ErbB expression pattern might be more informative than the expression level of one receptor regarding cancer prognosis and prediction of response to targeted therapies. Bispecific ligands could thus be used as imaging agents with prognostic value. Another aspect of dual targeting is the possibility of increased tumor specificity since tumors are more likely than healthy tissue to express high amounts of two receptors.
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- Hansson, Anders, 1953-, et al.
(författare)
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Two sides of the coin - general practitioners' experience of working in multidisciplinary teams.
- 2008
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Ingår i: Journal of interprofessional care. - : Informa UK Limited. - 1356-1820 .- 1469-9567. ; 22:1, s. 5-16
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Tidskriftsartikel (refereegranskat)abstract
- Multidisciplinary teamwork, defined as the collaboration between different professional groups to achieve a common purpose, is commonly regarded as a means to meet the complex tasks that medicine has to deal with today. However, many attempts to introduce the method in primary care have failed and this is supposed to be partly due to the fact that general practitioners (GPs) did not participate in the implementation of the method. The aim of this investigation was to get a deeper understanding of their attitude to teamwork by interviewing nine GPs at four Swedish health care centres, where successful teamwork had been ongoing since 1997. Themes and categories in the interviews were identified according to content analysis. Although the attitude in general was in favour of teamwork, four major themes: time-consuming versus time-saving; shared responsibility versus main responsibility; medical expert versus generalist; shared knowledge versus all knowing, could be identified, which all revealed ambivalence towards teamwork among the interviewees. It was concluded that, if teamwork is to be successfully introduced into primary care, the GPs' self-perception has to be taken into consideration as has the prestige and status associated with their traditional role and the benefits of teamwork to the profession of medicine. Apart from time, teamwork requires, professional supervision and doctors need to be trained in this method as early as in medical school.
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- Hansson, Anders, 1953-, et al.
(författare)
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Working together--primary care doctors' and nurses' attitudes to collaboration.
- 2010
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Ingår i: Scandinavian journal of public health. - : SAGE Publications. - 1651-1905 .- 1403-4948. ; 38:1, s. 78-85
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Tidskriftsartikel (refereegranskat)abstract
- Multidisciplinary teamwork is recommended for various disorders and it has been suggested that it is a way to meet the new challenges and demands facing general practitioners (GPs) in modern society. Attempts to introduce the method in primary care have failed partly due to GPs' unwillingness to participate. The aim of this study was to measure attitudes towards collaboration among GPs and district nurses (DN) and to investigate whether there is a correlation between a positive attitude toward collaboration and high self-esteem in the professional role.
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- Holm, Patrik, 1975-
(författare)
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Functional mapping and in vivo metabolism of the monoclonal antibody TS1 and its single-chain fragment : Its interaction with the antigen and the anti-idiotype
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Antibodies are proteins capable of specific interactions to a wide range of molecules. These interactions are facilitated by the complementary determining regions (CDR).Carcinomas are the most common of human cancers and they release significant amount of cytokeratins (CK) in the necrotic areas of the tumors. The CKs stay in the tumor, since they have low solubility. The antibody studied in this thesis, the anti-CK 8 antibody TS1, has shown to be effective in tumor targeting and is proposed to be useful in therapy.Single-chain antibodies (scFv) are recombinant antibodies which are much smaller than the intact IgG. This is an advantage when used in tumor therapy, since they can penetrate the tumors more easily than the larger IgG. Moreover, they are expressed by one single gene which make them easy to modify, for example by site-directed mutagenesis.The anti-idiotypic antibody αTS1 can be used to clear the TS1 form the circulation and thereby clear the body from non-tumor bound TS1 in therapy. To be able to modify the binding of an antibody to its antigen and or anti-idiotype, these interactions must be studied. In this study this is accomplished by chemical modifications of the IgGs TS1 and αTS1 and the antigen CK 8. Guided by these results, amino acid residues were mutated by using site-directed mutagenesis in the TS1-218 scFv and the effects were studied. From mutational study results, the functional epitope could be mapped and it was found that there are mainly tyrosines, but also charged residues, serine and a tryptophan that are important for both interactions. The binding of TS1-218 to both αTS1 and CK 8 could be improved by changing the negatively charged side-chains by mutations to their corresponding amide or alanine.Both the IgG and scFv versions of TS1 were administered in vivo. The IgG αTS1 was used to clear the TS1 from the circulation by forming immune complexes. The immune complexes, consisting of four or more antibodies, were mainly metabolized by the liver. The scFv TS1-218 could localize to the tumor in a tumor xenograft mouse model, although a higher uptake would be desired in a therapeutic strategy. The scFv was cleared rapidly by the kidneys, but the clearance could be slowed by pre-formed immune complexes with anti-TS1 scFv in vitro, prior to administration in vivo.
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- Pettersson, Monica, 1963, et al.
(författare)
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Experiences of Screening for Abdominal Aortic Aneurysm : In and Out on Five Minutes
- 2014
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Ingår i: Health. - : Scientific Research Publishing, Inc.. - 1949-4998 .- 1949-5005. ; 6, s. 1385-1395
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Tidskriftsartikel (refereegranskat)abstract
- Background: The purpose of AAA screening is to prevent rupture and mortality. Screening for life-threatening diseases is a double-edged sword. The aim of this study is to describe 65-year-old men's experiences of health related quality of life and anxiety after screening for Abdominal Aortic Aneurysm, and experiences of information and reasons for not participating. Methods: 368 men answered Short Form 36 (SF-36), and anxiety and depression scale (HAD). 72 telephone interviews were conducted with the participants and 77 with those who declined to take part in the screening programme. Results: The SF-36 domains of Physical Function and Role limitations due to emotional health problems were significantly better for men who had undergone screening compared to a matched population. Compared to non-smokers, smokers had lower values in the SF-36 domains of general health perceptions, social functioning, role limitations due to emotional health problems and mental health. 80% of patients did not experience any form of anxiety/panic in connection with the screening invitation. Of the men who did not participate, 56% stated that they would like to be screened or had already undergone the examination. Conclusion: The men who underwent the investigation were healthier in some of the SF-36 domains than the general population. The participants did not experience any great anxiety before the screening and despite the short duration of the examination.
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- Svenningsson, Irene, 1957, et al.
(författare)
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Anxiety and depression in obese and normal-weight individuals with diabetes type 2: A gender perspective
- 2012
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 1471-6712 .- 0283-9318. ; 26:2, s. 349-354
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Tidskriftsartikel (refereegranskat)abstract
- Background: Obesity is a problem that is increasing worldwide, leading to an increased incidence of type 2 diabetes mellitus (T2DM). Depression is more common among individuals with diabetes, and they are more likely than non-diabetic individuals to experience emotional problems. People with both T2DM and obesity bear an additional emotional burden, which affects their quality of life. Objectives: To describe the prevalence of symptoms of anxiety and depression in groups of obese and normal-weight individuals with T2DM who are undergoing primary care and to investigate possible differences between the groups and between genders. Method: Three hundred and thirty-nine patients with T2DM from nine primary-care centres participated in a cross-sectional study (n = 180 + 159). The response rate was 67%. The Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory – second edition (BDI-II) were employed to estimate the patients’ symptoms of depression and anxiety. Results: An association between T2DM, obesity and depression was observed in both genders. More than one in three women and one in five men with T2DM and obesity exhibited symptoms of anxiety or depression. In the normal-weight group, the females presented more symptoms of anxiety than did their male counterparts. Conclusion: In primary healthcare, the fact that both obese men and women with T2DM are at increased risk of anxiety and depression is an important finding, which must be recognised and considered in the course of primary healthcare consultations. Meeting the unique needs of each individual requires an understanding of both laboratory data and the individual’s emotional status.
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