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Sökning: WFRF:(Wingren G)

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1.
  • Lundgren, Fredrik, et al. (författare)
  • PTFE bypass to below-knee arteries : distal vein collar or not? A prospective randomised multicentre study
  • 2010
  • Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 39:6, s. 747-754
  • Tidskriftsartikel (refereegranskat)abstract
    • BackgroundPatency and limb salvage after synthetic bypass to the arteries below-knee are inferior to that which can be achieved with autologous vein. Use of a vein collar at the distal anastomosis has been suggested to improve patency and limb salvage, a problem that is analysed in this randomised clinical study.MethodsPatients with critical limb ischaemia undergoing polytetrafluoroethylene (PTFE) bypass to below-knee arteries were randomly either assigned a vein collar or not in two groups – bypass to the popliteal artery below-knee (femoro-popliteal below-knee (FemPopBK)) and more distal bypass (femoro-distal bypass (FemDist)). Follow-up was scheduled until amputation, death or at most 5 years, whichever event occurred first.ResultsIn the FemPopBK and in the FemDist groups, 115/202 and 72/150 were randomised to have a vein collar, respectively. Information was available for 345 of 352 randomised patients (98%).At 3 years, primary patency was 26% (95% confidence interval (CI) 18–38) with a vein collar and 43 (33–58) without a vein collar for femoro-popliteal bypass and 20 (11–38), and 17 (9–33) for femoro-distal bypass, respectively. The corresponding figures for limb salvage were 64 (54–75) and 61 (50–74) for femoro-popliteal bypass, and 59 (46–76) and 44 (32–61) for femoro-distal bypass with and without a vein collar, respectively. Log-rank-test for the whole Kaplan–Meier life table curve showed no statistically significant differences with or without vein collar primary patency: p = 0.0853, p = 0.228; secondary patency: p = 0.317, p = 0.280; limb salvage: p = 0.757, p = 0.187 for FemPopBK and FemDist, respectively. The use of a vein collar did not influence patency or limb salvage.ConclusionThis study failed to show any benefit for vein collar with PTFE bypass to a below-knee artery.
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  • Province, M. A., et al. (författare)
  • CYP2D6 Genotype and Adjuvant Tamoxifen : Meta-Analysis of Heterogeneous Study Populations
  • 2014
  • Ingår i: Clinical Pharmacology and Therapeutics. - New York, USA : Nature Publishing Group. - 0009-9236 .- 1532-6535. ; 95:2, s. 216-227
  • Tidskriftsartikel (refereegranskat)abstract
    • The International Tamoxifen Pharmacogenomics Consortium was established to address the controversy regarding cytochrome P450 2D6 (CYP2D6) status and clinical outcomes in tamoxifen therapy. We performed a meta-analysis on data from 4,973 tamoxifen-treated patients (12 globally distributed sites). Using strict eligibility requirements (postmenopausal women with estrogen receptor-positive breast cancer, receiving 20 mg/day tamoxifen for 5 years, criterion 1), CYP2D6 poor metabolizer status was associated with poorer invasive disease-free survival (IDFS: hazard ratio = 1.25; 95% confidence interval = 1.06, 1.47; P = 0.009). However, CYP2D6 status was not statistically significant when tamoxifen duration, menopausal status, and annual follow-up were not specified (criterion 2, n = 2,443; P = 0.25) or when no exclusions were applied (criterion 3, n = 4,935; P = 0.38). Although CYP2D6 is a strong predictor of IDFS using strict inclusion criteria, because the results are not robust to inclusion criteria (these were not defined a priori), prospective studies are necessary to fully establish the value of CYP2D6 genotyping in tamoxifen therapy.
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  • Annerback, Eva-Maria, et al. (författare)
  • Child physical abuse and concurrence of other types of child abuse in Sweden : Associations with health and risk behaviors
  • 2012
  • Ingår i: International Journal of Child Abuse & Neglect. - : Elsevier BV. - 0145-2134 .- 1873-7757. ; 36:7-8, s. 585-595
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To examine the associations between child physical abuse executed by a parent or caretaker and self-rated health problems/risk-taking behaviors among teenagers. Further to evaluate concurrence of other types of abuse and how these alone and in addition to child physical abuse were associated with bad health status and risk-taking behaviors.Methods: A population-based survey was carried out in 2008 among all the pupils in 2 different grades (15 respectively 17 years old) in Sodermanland County, Sweden (n = 7,262). The response rate was 81.8%. The pupils were asked among other things about their exposure to child physical abuse, exposure to parental intimate violence, bullying, and exposure to being forced to engage in sexual acts. Adjusted analyses were conducted to estimate associations between exposure and ill-health/risk-taking behaviors.Results: Child physical abuse was associated with poor health and risk-taking behaviors with adjusted odds ratios (OR) ranging from 1.6 to 6.2. The associations were stronger when the pupils reported repeated abuse with OR ranging from 2.0 to 13.2. Also experiencing parental intimate partner violence, bullying and being forced to engage in sexual acts was associated with poor health and risk-taking behaviors with the same graded relationship to repeated abuse. Finally there was a cumulative effect of multiple abuse in the form of being exposed to child physical abuse plus other types of abuse and the associations increased with the number of concurrent abuse.Conclusions: This study provides strong indications that child abuse is a serious public health problem based on the clear links seen between abuse and poor health and behavioral problems. Consistent with other studies showing a graded relationship between experiences of abuse and poor health/risk-taking behaviors our study shows poorer outcomes for repeated and multiple abuse. Thus, our study calls for improvement of methods of comprehensive assessments, interventions and treatment in all settings where professionals meet young people.
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4.
  • Stanezai, S., et al. (författare)
  • Higher intensity of Low Molecular Weight Protein Tyrosine Phosphatase/ ACP-1 in survivors of patients diagnosed with Diffuse Large B Cell Lymphoma (DLBCL) compared to non-survivors
  • 2016
  • Ingår i: Austin Biology. - : Austin Publishing. ; 1:2
  • Tidskriftsartikel (refereegranskat)abstract
    • Adult Diffuse Large B Cell Lymphoma (DLBCL) is a heterogeneous form of hematopoietic cancer and difficult to treat. In order to find a better diagnostic indication for the disease, we analyzed Low Molecular Weight Protein Tyrosine Phosphatase (LMWPTP) that in humans is encoded by the ACP1 gene. LMWPTP is an enzyme shown to counteract Protein Tyrosine Kinases (PTK) and was suggested to be a negative growth factor regulator. However, the 18 kDa PTP can also have a positive effect on cell growth and proliferation, indicating a controversial role in the tumorigenic process. LMWPTP exists in different isoforms which are electrophoretically, kinetically and immunologically distinct. We have studied two subgroups of DLBCL consisting of a Germinal Center B cell like (GCB) and a non-Germinal Center B cell like (non-GCB) group. The two subgroups have been defined by gene-expressing profiling and are associated with differential outcome. The expression levels of LMWPTP protein was compared and showed significant differences between the GCB and non- GCB subgroups (p=0.012). Interestingly, when the samples were divided into survivors and non-survivors, and thereafter analyzed for LMWPTP expression, the samples from patients with a higher survival rate showed increased staining intensity, whereas the samples from patients with lower intensity of LMWPTP did not survive the disease (p=0.001). In conclusion, we have shown that DLBCL patients with worse outcome express LMWPTP with a lower intensity, suggesting a tumor suppressor role for this form of the enzyme.
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5.
  • Andersson, Eva, 1955, et al. (författare)
  • A case-referent study of cancer mortality among sulfate mill workers in Sweden.
  • 2001
  • Ingår i: Occupational and environmental medicine. - 1351-0711. ; 58:5, s. 321-4
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To investigate whether workers in Swedish sulfate mills have an increased risk of death from certain malignancies that have previously been linked to the pulping process. METHODS: Subjects of the study (n=2480) were men aged 40-75 at death during 1960-89 in the parishes surrounding four sulfate mills. Exposure assessment was based on information from the personnel files in the mills- 35% of the subjects were recognised there, and work categories were created. RESULTS: Among all sulfate mill workers, the odds ratio (OR) (90% confidence interval (90% CI)) for death from lung cancer was 1.6 (1.1 to 2.3), pleural mesotheliomas 9.5 (1.9 to 48), brain tumours 2.6 (1.2 to 5.3), and liver or biliary tract cancer 2.3 (1.0 to 5.2). There was an increased mortality from leukaemia among workers in the soda recovery plant (5.9 (2.6 to 13)) and bleaching plant and digester house (2.8 (1.0 to 7.5)). CONCLUSIONS: Sulfate mill workers were at increased risk of dying from lung cancer and pleural mesotheliomas, probably due to exposure to asbestos. Increased risks of brain tumours and cancers of the liver or biliary tract were also found but the aetiology is not obvious.
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  • Andersson, Eva, 1955, et al. (författare)
  • Mortality from asthma and cancer among sulfite mill workers.
  • 1998
  • Ingår i: Scandinavian journal of work, environment & health. - 0355-3140. ; 24:1, s. 12-7
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: The aims of the present case-referent study were to investigate whether sulfite workers show increased mortality from asthma, chronic obstructive pulmonary disease or certain malignancies of interest in relation to sulfite mill work. The main exposure from the pulping processes is from sulfur dioxide, wood dust and terpenes. METHODS: The subjects of the study were all the men who died between 1960 and 1989 and who were aged 40 to 75 years at death (N = 780) in the parishes surrounding 3 sulfite mills. The men who died from asthma (N = 13), COPD (N = 20), lung cancer (N = 33), stomach cancer (N = 35), or brain tumor (N = 10) formed the case group. All the subjects, except the cases in question, were used as referents. As a proxy variable of exposure, job titles from the registers of deaths and burials were used, and 24% of the subjects were classified as exposed. RESULTS: There was an increased mortality from asthma [odds ratio(OR) 2.8, 90% confidence interval (90% CI) 1.1-6.8] and brain tumors (OR 3.3, 90% CI 1.2-8.9) among the sulfite workers. The mortality due to lung cancer was not significantly increased (OR 1.4, 90% CI 0.7-2.6), and there was a reduced mortality from stomach cancer (OR 0.4, 90% CI 0.2-0.9). CONCLUSIONS: The increased asthma mortality may be due to accidental exposure to irritating gases, such as sulfur dioxide. The increased risk for brain tumors has no obvious explanation.
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  • Delfani, P., et al. (författare)
  • Deciphering systemic lupus erythematosus-associated serum biomarkers reflecting apoptosis and disease activity
  • 2017
  • Ingår i: Lupus. - : SAGE Publications. - 0961-2033 .- 1477-0962. ; 26:4, s. 373-387
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE) is a severe chronic inflammatory autoimmune connective tissue disease. Despite major efforts, SLE remains a poorly understood disease with unpredictable course, unknown etiology and complex pathogenesis. Apoptosis combined with deficiency in clearing apoptotic cells is an important etiopathogenic event in SLE, which could contribute to the increased load of potential autoantigen(s); however, the lack of disease-specific protein signatures deciphering SLE and the underlying biological processes is striking and represents a key limitation. In this retrospective pilot study, we explored the immune system as a specific sensor for disease, in order to advance our understanding of SLE. To this end, we determined multiplexed serum protein expression profiles of crude SLE serum samples, using antibody microarrays. The aim was to identify differential immunoprofiles, or snapshots of the immune response modulated by the disease, reflecting apoptosis, a key process in the etiology of SLE and disease activity. The results showed that multiplexed panels of SLE-associated serum biomarkers could be decoded, in particular reflecting disease activity, but potentially the apoptosis process as well. While the former biomarkers could display a potential future use for prognosis, the latter biomarkers might help shed further light on the apoptosis process taking place in SLE.
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  • Eklund, Arne, et al. (författare)
  • Recurrent inguinal hernia : randomized multicenter trial comparing laparoscopic and Lichtenstein repair
  • 2007
  • Ingår i: Surgical Endoscopy. - : Springer Science and Business Media LLC. - 0930-2794 .- 1432-2218. ; 21:4, s. 634-640
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The optimal treatment for recurrent inguinal hernia is of concern due to the high frequency of recurrence. METHODS: This randomized multicenter study compared the short- and long-term results for recurrent inguinal hernia repair by either the laparoscopic transabdominal preperitoneal patch (TAPP) procedure or the Lichtenstein technique. RESULTS: A total of 147 patients underwent surgery (73 TAPP and 74 Lichtenstein). The operating time was 65 min (range, 23-165 min) for the TAPP group and 64 min (range, 25-135 min) for the Lichtenstein group. Patients who underwent TAPP reported significantly less postoperative pain and shorter sick leave (8 vs 16 days). The recurrence rate 5 years after surgery was 19% for the TAPP group and 18% for the Lichtenstein group. CONCLUSION: The short-term advantage for patients who undergo the laparoscopic technique is less postoperative pain and shorter sick leave. In the long term, no differences were observed in the chronic pain or recurrence rate.
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  • Jivegård, Lennart, 1950, et al. (författare)
  • Effects of three months of low molecular weight heparin (dalteparin) treatment after bypass surgery for lower limb ischemia--a randomised placebo-controlled double blind multicentre trial.
  • 2005
  • Ingår i: European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery. - : Elsevier BV. - 1078-5884. ; 29:2, s. 190-8
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To test the hypothesis that long-term postoperative dalteparin (Fragmin), Pharmacia Corp) treatment improves primary patency of peripheral arterial bypass grafts (PABG) in lower limb ischemia patients on acetylsalicylic acid (ASA) treatment. DESIGN: Prospective randomised double blind multicenter study. MATERIALS AND METHODS: Using a computer algorithm 284 patients with lower limb ischemia, most with pre-operative ischemic ulceration or partial gangrene, from 12 hospitals were randomised, after PABG, to 5000 IU dalteparin or placebo injections once daily for 3 months. All patients received 75 mg of ASA daily for 12 months. Graft patency was assessed at 1, 3 and 12 months. RESULTS: At 1 year, 42 patients had died or were lost to follow-up. Compliance with the injection schedule was 80%. Primary patency rate, in the dalteparin versus the control group, respectively, was 83 versus 80% (n.s.) at 3 months and 59% for both groups at 12 months. Major complication rates and cardiovascular morbidity were not different between the two groups. CONCLUSIONS: In patients on ASA treatment, long-term postoperative dalteparin treatment did not improve patency after peripheral artery bypass grafting. Therefore, low molecular weight heparin treatment cannot be recommended for routine use after bypass surgery for critical lower limb ischemia.
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  • Mellby, Linda D., et al. (författare)
  • Serum biomarker signature-based liquid biopsy for diagnosis of early-stage pancreatic cancer
  • 2018
  • Ingår i: Journal of Clinical Oncology. - 0732-183X. ; 36:28, s. 2887-2894
  • Tidskriftsartikel (refereegranskat)abstract
    • Purpose Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year survival of, 10% because of diffuse symptoms leading to late-stage diagnosis. That survival could increase significantly if localized tumors could be detected early. Therefore, we used multiparametric analysis of blood samples to obtain a novel biomarker signature of early-stage PDAC. The signature was derived from a large patient cohort, including patients with well-defined early-stage (I and II) PDAC. This biomarker signature was validated subsequently in an independent patient cohort. Patients and Methods The biomarker signature was derived from a case-control study, using a Scandinavian cohort, consisting of 16 patients with stage I, 132 patients with stage II, 65 patients with stage III, and 230 patients with stage IV PDAC, and 888 controls. This signature was validated subsequently in an independent case-control cohort in the United States with 15 patients with stage I, 75 patients with stage II, 15 patients with stage III, and 38 patients with stage IV PDAC, and 219 controls. An antibody microarray platform was used to identify the serum biomarker signature associated with early-stage PDAC. Results Using the Scandinavian case-control study, a biomarker signature was created, discriminating samples derived from patients with stage I and II from those from controls with a receiver operating characteristic area under the curve value of 0.96. This signature, consisting of 29 biomarkers, was then validated in an independent case-control study in the United States. The biomarker signature could discriminate patients with stage I and II PDAC from controls in this independent patient cohort with a receiver operating characteristic area under the curve value of 0.96. Conclusion This serum biomarker signature might represent a tenable approach to detecting early-stage, localized PDAC if these findings are supported by a prospective validation study.
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13.
  • Morales-Suarez-Varela, M.M., et al. (författare)
  • Occupational exposures and Mycosis Fungoides. A European multicentre case-control study (Europe)
  • 2005
  • Ingår i: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 0957-5243 .- 1573-7225. ; 16:10, s. 1253-1259
  • Tidskriftsartikel (refereegranskat)abstract
    • Objectives: Mycosis Fungoides (MF) is a rare disease with an occurrence indicating that occupational exposures may play a role. To estimate the association between MF and occupational exposures as measured by means of an job-exposure matrix (JEM). Methods: A European multicenter case-control study was conducted from 1995 to 1997 and included seven rare cancers, one of which was MF. Patients between 35 and 69 years of age, diagnosed with MF (n = 140), were recruited and the diagnoses were checked by a reference pathologist who classified 83 cases as definite, 35 cases as possible and 22 cases as not accepted. Among the 118 accepted cases, 104 cases were interviewed, of which 76 were definite cases. We selected population controls and colon cancer controls to serve all seven case groups. Altogether 833 colon cancer controls and 2071 population controls were interviewed. Based on the reported occupational experiences, a team of industrial hygiene specialists identified five potential exposures and developed an JEM. This JEM was used to estimate the odds ratios (OR) for MF as a function of these exposures. The JEM included aromatic and/or halogenated hydrocarbons (AAHs), chrome (VI) and its salts, electromagnetic radiations, silica and pesticides. Results: Exposures to AHHs (OR 6.3, C.I 2.4-16.7 for male) were associated with a high MF risk. Conclusions: The study supports the hypothesis that some MFs have an occupational etiology but only a small fraction of exposed workers are apparently susceptible since the disease is so rare. © Springer 2005.
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  • Morales-Suarez-Varela, M.M., et al. (författare)
  • Occupational sun exposure and mycosis fungoides : A european multicenter caseg-control study
  • 2006
  • Ingår i: Journal of Occupational and Environmental Medicine. - : Ovid Technologies (Wolters Kluwer Health). - 1076-2752 .- 1536-5948. ; 48:4, s. 390-393
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVE: We sought to study the association between occupational sun exposure and mycosis fungoides (MF), a peripheral T-cell lymphoma. SUBJECTS and METHODS: A European multicenter case-control study including seven rare cases (one being MF) was conducted between 1995 and 1997. From the 118 accepted cases, 104 were interviewed, of which 76 were definite cases. Population controls were selected randomly from the regions of case ascertainment. Information based on occupational experiences was coded according to industry types. A job exposure matrix was created according to the expected exposure to sunlight. RESULTS: Once exposures to aromatic halogenated hydrocarbons were eliminated (odds ratio = 2.3, 95% confidence interval = 0.9-6.2), a high MF risk was associated with exposures to solar radiation. CONCLUSION: It would appear that workers exposed to sunlight have a higher risk of MF. However, this factor is not the only one involved. Copyright © 2006 by American College of Occupational and Environmental Medicine.
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  • Tisell, L E, et al. (författare)
  • Improved survival of patients with papillary thyroid cancer after surgical microdissection.
  • 1996
  • Ingår i: World journal of surgery. - 0364-2313. ; 20:7, s. 854-9
  • Tidskriftsartikel (refereegranskat)abstract
    • A total of 195 patients had surgery for papillary thyroid cancer. The mean age at operation was 50 years. A microdissection technique was used for total thyroidectomy and lymph node clearance. Postoperative radioiodine tests showed no uptake or an uptake close to the background activity in 77% of the examined patients. By counting the lymph nodes removed at surgery we were able to check on the quality of the lymph node dissection. Men had a higher incidence (70%) of lymph node metastases than women (45%). Only 4% of the patients had radioiodine ablation of the thyroid remnant. The median follow-up time was 13 years. None of the patients below 45 years of age at surgery died of thyroid cancer. In the older age group eight patients died of thyroid cancer at a mean age of 75 years. Five of those who died of a thyroid carcinoma had distant metastases at diagnosis. Among patients with resectable disease, three (1.6%) died of thyroid cancer, all of whom had lived for more than 17 years after surgery. Hence longer follow-up is needed before we know the final mortality in our series. The results suggest that surgical technique and strategy can positively influence the survival of patients with papillary thyroid cancer.
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22.
  • Wang, Tianyan, et al. (författare)
  • PIP5K1α is Required for Promoting Tumor Progression in Castration-Resistant Prostate Cancer
  • 2022
  • Ingår i: Frontiers in Cell and Developmental Biology. - : Frontiers Media S.A.. - 2296-634X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • PIP5K1α has emerged as a promising drug target for the treatment of castration-resistant prostate cancer (CRPC), as it acts upstream of the PI3K/AKT signaling pathway to promote prostate cancer (PCa) growth, survival and invasion. However, little is known of the molecular actions of PIP5K1α in this process. Here, we show that siRNA-mediated knockdown of PIP5K1α and blockade of PIP5K1α action using its small molecule inhibitor ISA-2011B suppress growth and invasion of CRPC cells. We demonstrate that targeted deletion of the N-terminal domain of PIP5K1α in CRPC cells results in reduced growth and migratory ability of cancer cells. Further, the xenograft tumors lacking the N-terminal domain of PIP5K1α exhibited reduced tumor growth and aggressiveness in xenograft mice as compared to that of controls. The N-terminal domain of PIP5K1α is required for regulation of mRNA expression and protein stability of PIP5K1α. This suggests that the expression and oncogenic activity of PIP5K1α are in part dependent on its N-terminal domain. We further show that PIP5K1α acts as an upstream regulator of the androgen receptor (AR) and AR target genes including CDK1 and MMP9 that are key factors promoting growth, survival and invasion of PCa cells. ISA-2011B exhibited a significant inhibitory effect on AR target genes including CDK1 and MMP9 in CRPC cells with wild-type PIP5K1α and in CRPC cells lacking the N-terminal domain of PIP5K1α. These results indicate that the growth of PIP5K1α-dependent tumors is in part dependent on the integrity of the N-terminal sequence of this kinase. Our study identifies a novel functional mechanism involving PIP5K1α, confirming that PIP5K1α is an intriguing target for cancer treatment, especially for treatment of CRPC.
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23.
  • Wegman, Pia, et al. (författare)
  • Expression of the forkhead transcription factor FOXL2 correlates with good prognosis in breast cancer patients treated with tamoxifen
  • 2011
  • Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 38:4, s. 1145-1151
  • Tidskriftsartikel (refereegranskat)abstract
    • Aromatase is an important enzyme in the local synthesis of oestrogens and its expression has been shown to be increased in breast cancer through the activation of multiple promoters. However, the mechanisms behind this are not yet fully understood. A novel candidate in this context is the transcription factor forkhead box L2 (FOXL2), which has been recognised to be co-expressed with aromatase and transcriptionally active promoter 11 in developing goat and chicken ovaries. We propose that FOXL2 could be involved in the increased expression of aromatase in breast cancer. We examined FOXL2 and its relation to aromatase in 132 postmenopausal breast cancer patients by immunohistochemistry. Using in silico analysis, we further searched for FOXL2 binding-elements in the aromatase gene promoters. The results demonstrate that FOXL2 is expressed in breast cancer and influences clinical outcome with improved recurrence-free survival in cases with nuclear expression. In a multivariate Cox model, nuclear FOXL2 was a significant prognostic factor in ER-positive patients treated with tamoxifen (HR=0.18, 95% confidence interval (CI)=0.04-0.81, P=0.03). Tumours expressing nuclear FOXL2 were also more likely positive for stromal and/or cytoplasmic aromatase (P=0.03 and P=0.008, respectively). In silico analyses revealed binding elements of FOXL2 in promoters 1.3, 11 and 17 of the aromatase gene of which promoter 1.7 was most significant. In conclusion, this is the first study to report that FOXL2 is expressed in breast cancer and correlates with aromatase as well as with clinical outcome. The results further strengthen a possible binding of FOXL2 to aromatase promoter 1.7. Nevertheless, whether FOXL2 is a direct activator of aromatase requires further investigation.
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  • Wingren, Christer, et al. (författare)
  • Antigen-binding sites dominate the surface properties of IgG antibodies
  • 1995
  • Ingår i: Molecular Immunology. - 1872-9142 .- 0161-5890. ; 32:11, s. 819-827
  • Tidskriftsartikel (refereegranskat)abstract
    • A new technique, liquid-liquid partition chromatography in an aqueous polyethylene glycol-dextran two-phase system, was used to detect differences in surface properties of antibodies with different antigen-binding sites. Employing well-characterized monoclonal IgG antibodies and Fab and Fc fragments thereof as well as chimeric IgG antibodies we found a remarkable relationship between structure of the antibody combining site and chromatographic behaviour. The surface properties of the IgG antibodies were dominated by those of its antigen-binding regions. In addition, our results indicated that the constant parts of the IgGs form similar scaffoldings, on to which CDRs of variable shapes and sizes are interspaced and constitute the major dominant differences in exposed surface properties.
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  • Wingren, Christer, et al. (författare)
  • Comparison of Surface Properties of Human IgA, IgE, IgG and IgM Antibodies with Identical and Different Specificities
  • 1996
  • Ingår i: Scandinavian Journal of Immunology. - : Wiley. - 1365-3083 .- 0300-9475. ; 44:5, s. 430-436
  • Tidskriftsartikel (refereegranskat)abstract
    • In this paper, the authors report the use of liquid-liquid partition chromatography (LLPC) in an aqueous polyethylene glycol (PEG)/dextran two-phase system to compare the surface properties (partition properties) of human antibodies and fragments thereof. The surface properties of all the monoclonal antibodies of different classes and subclasses investigated were within the same broad range as that observed for the polyclonal antibodies and no relationship was found between the exposed surfaces of the immunoglobulins (Ig) and their heavy chain isotype. Moreover, Fc fragments from various IgG1, 2 and 4 myeloma proteins were found to exhibit similar surface properties. Employing chimeric antibodies with identical variable regions the authors found that intact IgG1, 2 and 4 displayed identical surface properties, while the corresponding IgA1, IgA2, IgG3, IgE and IgM antibodies differed both from each other and from the IgGs. The surface properties of chimeric IgG3 could be made similar to those of the IgG1, 2 and 4 chimers by partially reducing the length of the hinge section, but new differences in surface properties appeared when their hinges were of similar length. Thus, LLPC can be used to detect differences or similarities in the surface properties of the antigen-binding regions as well as the Fc part in the various isotypes. This can shed light on biological activities such as antigen binding and effector function.
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