| 1. |
- Adolfsson, Emma, 1977-, et al.
(författare)
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Bone marrow- and adipose tissue-derived mesenchymal stem cells from donors with coronary artery disease : growth, yield, gene expression and the effect of oxygen concentration
- 2020
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Ingår i: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 80:4, s. 318-326
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Tidskriftsartikel (refereegranskat)abstract
- Mesenchymal stem cells (MSCs) for cardiovascular cell therapy are procured from different sources including bone marrow and adipose tissue. Differently located MSCs differ in growth potential, differentiation ability and gene expression when cultured in vitro, and studies show different healing abilities for different MSC subgroups. In this study, bone marrow derived MSCs (BMSCs) and adipose tissue derived MSCs (ADSCs) from six human donors with coronary artery disease were compared for growth potential and expression of target genes (Angpt1, LIF, HGF, TGF-β1 and VEGF-A) in response to exposure to 1% and 5% O2, for up to 48 h. We found greater growth of ADSCs compared to BMSCs. ADSCs expressed higher levels of Angpt1, LIF and TGF-β1 and equal levels of VEGF-A and HGF as BMSCs. In BMSCs, exposure to low oxygen resulted in upregulation of TGF-β1, whereas other target genes were unaffected. Upregulation was only present at 1% O2. In ADSCs, LIF was upregulated in both oxygen concentrations, whereas Angpt1 was upregulated only at 1% O2. Different response to reduced oxygen culture conditions is of relevance when expanding cells in vitro prior to administration. These findings indicate ADSCs as better suited for cardiovascular cell therapy compared to BMSCs.
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| 2. |
- Berg von Linde, Maria, et al.
(författare)
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Expression of Paracrine Effectors in Human Adipose-Derived Mesenchymal Stem Cells Treated With Plasma From Brown Bears (Ursus arctos)
- 2021
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Ingår i: Clinical and Translational Science. - : Wiley-Blackwell Publishing Inc.. - 1752-8054 .- 1752-8062. ; 14:1, s. 317-325
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Tidskriftsartikel (refereegranskat)abstract
- Adipose-derived mesenchymal stem cells (ADSCs) are promising candidates for novel cell therapeutic applications. Hibernating brown bears sustain tissue integrity and function via unknown mechanisms, which might be plasma borne. We hypothesized that plasma from hibernating bears may increase the expression of favorable factors from human ADSCs. In an experimental study, ADSCs from patients with ischemic heart disease were treated with interventional media containing plasma from hibernating and active bears, respectively, and with control medium. Extracted RNA from the ADSCs was sequenced using next generation sequencing. Statistical analyses of differentially expressed genes were performed using fold change analysis, pathway analysis, and gene ontology. As a result, we found that genes associated with inflammation, such as IGF1, PGF, IL11, and TGFA, were downregulated by > 10-fold in ADSCs treated with winter plasma compared with control. Genes important for cardiovascular development, ADM, ANGPTL4, and APOL3, were upregulated in ADSCs when treated with winter plasma compared with summer plasma. ADSCs treated with bear plasma, regardless if it was from hibernating or active bears, showed downregulation of IGF1, PGF, IL11, INHBA, IER3, and HMOX1 compared with control, suggesting reduced cell growth and differentiation. This can be summarized in the conclusion that plasma from hibernating bears suppresses inflammatory genes and activates genes associated with cardiovascular development in human ADSCs. Identifying the involved regulator(s) holds therapeutic potential.
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| 3. |
- Bergengren, Lovisa, 1972-
(författare)
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Cervical screening with primary HPV : from research to clinical effectiveness
- 2020
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Organized cervical screening has greatly reduced the incidence of cervical cancer where implemented. Human papilloma virus (HPV) is the cause of cervical cancer, and in later years, convincing evidence has led to cervical screening with HPV as the primary method being implemented around the world. The overall aim of this thesis is to improve cervical screening, with focus on HPV screening.Papers I–III were performed with focus on postmenopausal women. Women aged, 55–59 years, excluded from the screening with a normal cytology cervical sample were found to have a high-risk HPV (hrHPV) prevalence of 5.5% in paper II. In a follow-up sample, 56% (71/126) had a persistent infection with the same genotype. Nineteen per cent of the women had dysplasia, where the majority of the high-grade squamous intraepithelial lesions (HSILs) were associated with HPV types other than HPV 16/18.Women 55-59 has a lower attendance rate in the study region, and since self-sample has been proven to increase attendance, paper I was performed to compare self-sample and professionally collected samples in these postmenopausal women. The concordance between the sampling methods was 83%, and both tests detected all histological HSILs. When including a study with older women (aged 70 years) in paper III, 23% of histological HSILs were found in hrHPV-positive women.Paper IV is a scientific evaluation of an implemented HPV-based screening programme, comparing clinical effectiveness and cost with cytology screening. More HSIL+ were detected in the new programme but at a higher cost than the old cytology-based programme. The screening visits for sampling accounted for two thirds of the costs.Altogether, the results indicate the importance of having a negative HPVtest before exiting screening. Data also present the necessity to find biomarkers that are more specific than cytology and HPV 16/18 for triaging women with hrHPV to further follow-up, both among postmenopausal women and other age groups when screening with HPV, since many women without HSIL are coming for clinical follow-up and treatment. Extending the screening interval between hrHPV-negative tests as well as implementing selfsampling to a greater extent can be important changes, since two thirds of the costs in the programme come from screening visits for sampling.
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| 4. |
- Bergengren, Lovisa, 1971-, et al.
(författare)
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Comparison between professional sampling and self-sampling for HPV-based cervical cancer screening among postmenopausal women
- 2018
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Ingår i: International Journal of Gynecology & Obstetrics. - : Wiley-Blackwell Publishing Inc.. - 0020-7292 .- 1879-3479. ; 142:3, s. 359-364
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate whether self-sampling is as reliable as professional sampling for HPV testing and genotype detection among postmenopausal women.METHODS: In the present prospective cross-sectional study, women in Örebro County, Sweden, who had high-risk HPV (hrHPV) and normal cytology results in exit screening tests conducted in between January 1, 2012, and December 31, 2014, were invited to follow-up screenings between February 24, 2015 and May 15, 2015, that included professional sampling and self-sampling. HPV genotypes were identified by a DNA-based assay that could detect 35 HPV genotypes. Findings between the different sampling methods were compared.RESULTS: Of 143 women who participated, 119 returned a self-sample. Completely concordant results were observed in 67 of these samples when both hrHPV and low-risk HPV genotypes were analyzed. Overall, 99 (83.2%) women had the same clinically relevant finding from both sampling methods. Twenty women had discordant hrHPV results (hrHPV detected in 10 self-samples vs 10 professionally collected samples; Cohen κ 0.66, 95% confidence interval 0.53-0.80). There was no significant difference between the two sampling methods for clinically significant infections (P>0.99) or extended genotyping (P=0.827).CONCLUSION: Postmenopausal women could be offered self-sampling devices to increase screening-program coverage while maintaining test quality.
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| 5. |
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| 6. |
- Bergengren, Lovisa, 1972-, et al.
(författare)
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Effectiveness and costs of an implemented primary HPV cervical screening programme in Sweden : A population based cohort study
- 2022
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Ingår i: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 25
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Tidskriftsartikel (refereegranskat)abstract
- Swedish guidelines recommend cervical screening with primary HPV for women ≥ 30 years of age. The aim of this study was to compare an implemented HPV cervical screening programme in the Region of Örebro County from September 1, 2016, with the former cytology-based screening programme.The clinical effectiveness by means of number of high-grade squamous intraepithelial lesions (HSILs) and cervical cancer cases detected in histology within 12 months after the screening test, together with cost implications were the main outcomes. Data were retrieved from the Swedish National Cervical Screening Registry between the years 2014-2015 (cytology based screening) and 2017-2018(HPV based screening), including screening information such as invitations and cytology and histology diagnoses.The detection rate of HSIL + among women ≥ 30 years of age was 1.2 times higher with HPV screening, but data revealed an increase in direct colposcopy referral rate by 54% and a higher percentage of irrelevant findings (≤LSIL). Screening based on HPV for women ≥ 30 has increased yearly cost from 1 to 1.3 million EUR, while increasing the number of HSIL + identified. Two thirds of the total costs are from visits for screening samples in the programme.HPV screening detected more cases of HSIL + compared to cytology screening among women ≥ 30 although high colposcopy rate, high rate of clinical irrelevant findings and higher costs were shown in the HPV-based screening programme, which implies that alterations in the screening programme in the future are important to consider.
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| 7. |
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| 8. |
- Bergengren, Lovisa, 1971-, et al.
(författare)
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HPV-based screening for cervical cancer among women 55-59 years of age
- 2019
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 14:6
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Many cervical cancers occurs among women over 65 and prevalence of HPV genotypes in this age cohort is sparingly studied. One aim of this study was to study the prevalence and distribution of HPV genotypes in women 55-59 years, with normal cytology when exiting the screening program. Secondly, HPV clearance as well as the value of HPV genotyping and/or liquid based cytology as triage tests for identifying histological dysplasia among women with persistent HPV was studied.METHODS: Women that exited the screening program with normal cytology, between the years 2012-2014, in Örebro County, Sweden, were invited to this study. A total of 2946 samples were analyzed with a broad-spectrum assay to detect both hrHPV and lrHPV in order to investigate the distribution of genotypes. In the consent group, women with a positive hrHPV test were offered a follow-up test and a cone biopsy for histological confirmation, and a follow up sample 6 months post cone.RESULTS: The overall prevalence of hrHPV was 7.4% and 59% of them remained hrHPV positive in a follow-up test after 12 months. A total of 99 women had a cone biopsy done, where 19% showed histological dysplasia. HPV 53 was the most common genotype, and among women with histology confirmed LSIL or HSIL, HPV 31 was most common. A positive hrHPV result showed a PPV of 25% for LSIL+ and 12.5%for HSIL+. Using detection of HPV 16/18 genotypes as a triage test for hrHPV positive tests, indicated FNR for histological LSIL+ and HSIL+ of 94% and 87.5% respectively, whilst triage based on cervical cytology had a FNR of 69% for LSIL+ and 37.5% for HSIL+.CONCLUSION: The most common hrHPV genotypes among women 55-59 years of age were non HPV16/18 genotypes, and in this population, these genotypes represented most of the histological verified HSIL lesions. This result does not support the proposition of a HPV 16/18 triaging test after a positive hrHPV test as a marker of histological HSIL+ cervical lesions in women over 55 years of age. Similarly, cytological triage after a positive hrHPV showed no additional benefit in this population. Specific triaging tests should be validated to follow post-menopausal women with a positive hrHPV test.
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| 9. |
- Bergengren, Lovisa, 1971-, et al.
(författare)
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Prevalence of HPV and pathological changes among women 70 years of age, 10 years after exclusion from the Swedish cervical cancer screening program
- 2020
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Ingår i: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 31:4, s. 377-381
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Örebro County introduced an updated screening program 2016 with primary HPV test for women over 30 years and prolonged screening, increasing the cut-off age from 56-60 to 64-70. The aim of this study was to investigate the prevalence of HPV genotypes and their correlation to histological changes in women, 10 years after exclusion from the screening program, due to an eventual implementation of a catch-up program including all women aged 60-70.METHODS: All women in Örebro County, born 1,946 (n = 1,968), were invited to a liquid-based cell sample with primary HPV screening. Samples were analyzed for hrHPV mRNA and positive samples were genotyped. hrHPV positive women were offered to do a conization.RESULTS: Out of 809 participants, 31 (3.8%) were hrHPV positive, of these 22 did a conization. Histologically, 5/22 (23%) had LSIL and 5/22 (23%) had HSIL. Normal histology was found in 12/22 (55%). The most prevalent genotypes were HPV 16, 33, 52, 56, and 68. Of the women with HSIL, one case of cervical cancer was confirmed in a recone biopsy after 4 months.CONCLUSION: The study showed considerable prevalence of hrHPV and histologically confirmed LSIL/HSIL. These data led to catch-up screening for women between 60 and 70 years when overlapping two screening strategies.
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| 10. |
- Botling, Johan, et al.
(författare)
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Biomarker Discovery in Non-Small Cell Lung Cancer : Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation
- 2013
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Ingår i: Clinical Cancer Research. - 1078-0432 .- 1557-3265. ; 19:1, s. 194-204
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.
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