| 1. |
- Koskela, Anita, 1979-, et al.
(author)
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Evaluation of Microsatellite instability score from GMS560 DNA panel
- 2022
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Conference paper (other academic/artistic)abstract
- Microsatellite instability is characterised by gains or losses of nucleotides in short tandem repeat sequences, microsatellites, dispersed throughout the human genome. Microsatellite instability status is a molecular fingerprint for DNA mismatch repair deficiency. Clinical detection of microsatellite instability status is important for identifying inherited disease in patients with colorectal and endometrial cancer but has also a prognostic value for survival and prediction of treatment response. Lately, microsatellite instability has been used as a tumor agnostic biomarker that predicts response to immune checkpoint inhibitors. To identify microsatellite instability status clinically, PCR and immunohistochemistry have been the gold standard. On the contrary, next generation sequencing provide simultaneous accession of large number of microsatellite loci and can be combined with detection of several other biomarkers. The national collaboration Genome Medicine Sweden have developed a solid tumour gene panel composed of 560 cancer associated genes with integrated microsatellite instability score. Our aim was to validate the microsatellite instability status based on microsatellite instability score from GMS560 DNA panel against the clinically used methods. Extracted DNA (100 ng) from formalin fixed paraffin embedded tissue sections with various tumour cell content >10% were analysed. During target enrichment sequencing analysis, allelic distribution from 5000 microsatellite markers were calculated by MSIsensor Pro to generate an instability score. The cohort consisted of microsatellite instable verified colorectal cancer samples (n=20), microsatellite stable solid tumour material (n=60). Preliminary results generated a microsatellite instability score for the colorectal cancer samples with a mean of 26.5 % (CI: 23.4-29.6, range: 16.9-32.3). Microsatellite stable tumour samples had a mean microsatellite instability score of 1.5 % (CI: 0.93-2.07, range: 1-4.45). In conclusion, we found the microsatellite instability score from GMS560 DNA panel to be both diagnostically sensitive and specific for determining MSI status due to obvious separation in instability.
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| 2. |
- Adolfsson, Emma, 1977-, et al.
(author)
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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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In: Scandinavian Journal of Clinical and Laboratory Investigation. - : Taylor & Francis. - 0036-5513 .- 1502-7686. ; 80:4, s. 318-326
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Journal article (peer-reviewed)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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| 3. |
- Berg von Linde, Maria, et al.
(author)
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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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In: Clinical and Translational Science. - : Wiley-Blackwell Publishing Inc.. - 1752-8054 .- 1752-8062. ; 14:1, s. 317-325
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Journal article (peer-reviewed)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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| 4. |
- Bergengren, Lovisa, 1972-
(author)
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Cervical screening with primary HPV : from research to clinical effectiveness
- 2020
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Doctoral thesis (other academic/artistic)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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| 5. |
- Bergengren, Lovisa, 1971-, et al.
(author)
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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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In: International Journal of Gynecology & Obstetrics. - : Wiley-Blackwell Publishing Inc.. - 0020-7292 .- 1879-3479. ; 142:3, s. 359-364
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Journal article (peer-reviewed)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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| 6. |
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| 7. |
- Bergengren, Lovisa, 1972-, et al.
(author)
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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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In: Preventive Medicine Reports. - : Elsevier. - 2211-3355. ; 25
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Journal article (peer-reviewed)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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| 8. |
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| 9. |
- Bergengren, Lovisa, 1971-, et al.
(author)
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HPV-based screening for cervical cancer among women 55-59 years of age
- 2019
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In: PLOS ONE. - : PLOS. - 1932-6203. ; 14:6
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Journal article (peer-reviewed)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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| 10. |
- Bergengren, Lovisa, 1971-, et al.
(author)
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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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In: Cancer Causes and Control. - : Springer. - 0957-5243 .- 1573-7225. ; 31:4, s. 377-381
-
Journal article (peer-reviewed)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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| 11. |
- Bäckdahl, Henrik, 1977, et al.
(author)
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Mechanical properties of bacterial cellulose and interactions with smooth muscle cells
- 2006
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In: Biomaterials. - : Elsevier BV. - 0142-9612 .- 1878-5905. ; 27:9, s. 2141-2149
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Journal article (peer-reviewed)abstract
- Tissue engineered blood vessels (TEBV) represent an attractive approach for overcoming reconstructive problems associated with vascular diseases by providing small calibre vascular grafts. The aim of this study has been to evaluate a novel biomaterial, bacterial cellulose (BC), as a potential scaffold for TEBV. The morphology of the BC pellicle grown in static culture was investigated with SEM. Mechanical properties of BC were measured in Krebs solution and compared with the properties of porcine carotid arteries and ePTFE grafts. Attachment, proliferation and ingrowth of human smooth muscle cells (SMC) on the BC were analysed in vitro. The BC pellicle had an asymmetric structure composed of a fine network of nanofibrils similar to a collagen network. The shape of the stress-strain response of BC is reminiscent of the stress-strain response of the carotid artery, most probably due to the similarity in architecture of the nanofibrill networks. SMC adhered to and proliferated on the BC pellicle; an ingrowth of up to 40 microm was seen after 2 weeks of culture. BC exhibit attractive properties for use in future TEBV.
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| 12. |
- Carlsson, Jessica, 1984-, et al.
(author)
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Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate
- 2013
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In: BMC Cancer. - London, United Kingdom : BioMed Central (BMC). - 1471-2407. ; 13
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Journal article (peer-reviewed)abstract
- Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate. Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers. Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified. Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.
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| 13. |
- Edsjö, Anders, et al.
(author)
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Molekylär patologi : nyckeln till målinriktad cancerbehandling [Molecular pathology - the key to precision oncology]
- 2021
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In: Läkartidningen. - : Läkartidningen Förlag AB. - 0023-7205 .- 1652-7518. ; 118
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Journal article (peer-reviewed)abstract
- Rapidly expanding knowledge of the molecular landscape of cancers has resulted in the implementation of an increasing number of specific therapies targeted at tumors with specific molecular aberrations. In response to this development, new tools for predictive testing for molecular targets need to be implemented in routine health care. To achieve robust future molecular diagnostic pathology, and equal opportunity for patients to qualify for targeted therapy, the national working group for Solid Tumors in the initiative Genomic Medicine Sweden (GMS) aims to implement regional and national platforms for comprehensive genomic tumor profiling and linked analysis pipelines. Novel IT-infrastrucutures and recruitment of bioinformaticians and molecular biologists to hospital labotatories are paramount. The infrastructure will allow wider inclusion into clinical trials and supplement the national cancer registries with molecular »real world data« for research and evaluation of implemented cancer therapies and diagnostic procedures.
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| 14. |
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| 15. |
- Gunaltay, Sezin, 1986-, et al.
(author)
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Oligoclonal T-cell Receptor Repertoire in Colonic Biopsies of Patients with Microscopic Colitis and Ulcerative Colitis
- 2017
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In: Inflammatory Bowel Diseases. - : Lippincott Williams & Wilkins. - 1078-0998 .- 1536-4844. ; 23:6, s. 932-945
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Journal article (peer-reviewed)abstract
- Background: Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.Methods: To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCR beta) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with non-inflamed colons using next-generation sequencing.Results: Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVb-Jb gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVb-Jb clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVb-Jb gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.Conclusions: Altogether, patients with MC and UC showed an oligoclonal TCRb distribution. TCRVb-Jb clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.
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| 16. |
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| 17. |
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| 18. |
- Helenius, Gisela, 1973, et al.
(author)
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Effect of shear stress on the expression of coagulation and fibrinolytic factors in both smooth muscle and endothelial cells in a co-culture model.
- 2008
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In: European surgical research. Europ?ische chirurgische Forschung. Recherches chirurgicales europ?ennes. - : S. Karger AG. - 1421-9921 .- 0014-312X. ; 40:4, s. 325-32
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Journal article (peer-reviewed)abstract
- Blood vessels are subjected to forces due to the flow. Endothelial cells (EC) are recipients, cross-talk with smooth muscle cells (SMC), and regulate physiology. It was hypothesized that both EC and SMC respond to shear stress, which alters the expression of factors in coagulation and fibrinolysis. METHODS: A co-culture of human saphenous vein EC (HSVEC) and human saphenous vein SMC (HSVSMC) was exposed to shear, following which the cells were separated. Gene expression of tissue factor, thrombomodulin (TM), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and urokinase plasminogen activator (uPA) were analyzed with real-time RT-PCR. Protein expression was studied with ELISA. In HSVEC, the expression of PAI-1 (x2.1), tPA (x1.8), uPA (x1.6), tissue factor (x2.5) and TM (x1.9) was upregulated after 4 h of shear compared to controls. After 24 h of shear, expression was still upregulated in tPA (x2.3) and TM (x1.6). In HSVSMC, change in expression of PAI-1 (x2.1) was present after 4 h and in uPA (x2.1), and TM (x0.4) after 24 h. Both HSVEC and HSVSMC responded to shear, which led to altered expression of coagulation and fibrinolytic factors. This indicates that SMC, and interactions between EC and SMC, are more important in the regulation of vascular wall hemostasis than earlier studies have reported.
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| 19. |
- Helenius, Gisela, 1973, et al.
(author)
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Expression of fibrinolytic and coagulation factors in cocultured human endothelial and smooth muscle cells
- 2004
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In: Tissue engineering. - 1076-3279. ; 10:3-4, s. 353-60
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Journal article (peer-reviewed)abstract
- Interactions between endothelial cells and smooth muscle cells are interesting from a tissue-engineering point of view. We have developed a coculture system that allows direct contact between these two cell types. The fibrinolytic factors PAI-1, tPA, and uPA and the coagulation factor TF, were studied at the gene level by RT-PCR and at the protein level by ELISA. Significant changes of all studied factors were seen at the gene level in cocultured endothelial cells. tPA and TF were upregulated 4- and 7-fold, respectively, and PAI-1 and uPA were downregulated 4- and 1.5-fold, respectively, compared with single-cultured controls. In cocultured smooth muscle cells alterations of PAI-1 and TF were significant, with a 1.5-fold upregulation of PAI-1 and a 2.5-fold downregulation of TF. Results at the protein level mirrored the gene expression results. These findings indicate that cocultured endothelial cells are rendered both hypercoagulative and hyperfibrinolytic.
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| 20. |
- Helenius, Gisela, 1973, et al.
(author)
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In vivo biocompatibility of bacterial cellulose
- 2006
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In: Journal of biomedical materials research. - : Wiley. - 1549-3296 .- 1552-4965. ; 76:2, s. 431-8
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Journal article (peer-reviewed)abstract
- The biocompatibility of a scaffold for tissue engineered constructs is essential for the outcome. Bacterial cellulose (BC) consists of completely pure cellulose nanofibrils synthesized by Acetobacter xylinum. BC has high mechanical strength and can be shaped into three-dimensional structures. Cellulose-based materials induce negligible foreign body and inflammatory responses and are considered as biocompatible. The in vivo biocompatibility of BC has never been evaluated systematically. Thus, in the development of tissue engineered constructs with a BC scaffold, it is necessary to evaluate the in vivo biocompatibility. BC was implanted subcutaneously in rats for 1, 4, and 12 weeks. The implants were evaluated in aspects of chronic inflammation, foreign body responses, cell ingrowth, and angiogenesis, using histology, immunohistochemistry, and electron microscopy. There were no macroscopic signs of inflammation around the implants. There were no microscopic signs of inflammation either (i.e., a high number of small cells around the implants or the blood vessels). No fibrotic capsule or giant cells were present. Fibroblasts infiltrated BC, which was well integrated into the host tissue, and did not elicit any chronic inflammatory reactions. The biocompatibility of BC is good and the material has potential to be used as a scaffold in tissue engineering.
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| 21. |
- Helenius, Gisela, 1973-, et al.
(author)
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Molecular triage of cervical screening samples in women 55-59 years of age : a pilot study
- 2023
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In: Infectious Agents and Cancer. - : BioMed Central (BMC). - 1750-9378. ; 18:1
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Journal article (peer-reviewed)abstract
- BACKGROUND: With HPV screening the specificity of screening positives has decreased, even with a cytological triage test. Increases in colposcopies and detection of benign or low-grade dysplasia are reported, not least in older women. These results highlight the necessity to find other triage tests in HPV screening strategies, so that women can be more accurately selected for colposcopy, thus minimizing the clinically irrelevant findings.METHODS: The study included 55- to 59-year-old women who exited the screening with normal cytology, but later in a follow-up test were positive for the HPV genotypes 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66 and 68 and had a cervical cone biopsy done. To model a screening situation with hrHPV-positive women, three different triage strategies, namely, cytology, genotyping and methylation, were performed. The study considered the effect of direct referral to colposcopy for HPV genotypes 16, 18, 31, 33, 45, 52 and 58, and methylation for FAM19A4 and hsa-mir124-2 and/or any form of abnormal cytology.RESULTS: Seven out of 49 women aged 55-59 years with hrHPV had a cone biopsy with high-grade squamous intraepithelial lesion. No triage method found all cases, and when comparing positive and negative predictive value and false negative rate, cytology showed better results than genotyping and methylation.CONCLUSION: This study does not support a switch in triage strategies from cytology to hrHPV genotyping and methylation for women above 55 years of age yet, but demonstrates the need for more evidence on molecular triage strategies.
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| 22. |
- Helenius, Gisela, 1973-, et al.
(author)
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Preliminary data from a Swedish self-sampling study in postmenopausal women
- 2019
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Conference paper (other academic/artistic)abstract
- Background: An updated screening algorithm was introduced in Sweden 2015. Primary HPV test for women >30 years old and a prolonged screening with the last test after 64 years of age were some of the changes. In the region of Örebro County, the previous cut-off age was 60 years and with a screening interval of 5 years, women left their last sample when they were 55-59 years old. In the shift between two screening programs, a group of women, 60-64 years old, that left the program 5-10 years ago were now included in the new screening. For re-inclusion, a two year long program was formed to catch-up this group of women and screen them according to the new screening algorithm. At the same time a research project investigating self-sampling was launched. At the same time as the women were invited for a last screening sample they were also asked to participate in a study where they should take a vaginal self-test up to one week after their ordinary screening sample was taken by a midwife.Method: Postmenopausal women between 64-70 years was included in the study. HPV status in samples from midwife sampling (MS) was compared to self-sampling (SS) samples. HPV was analyzed using HPV Aptima and all HPV positive samples, independent of sampling method, was triaged with cytology and followed-up according to national guidelines.Results: So far, 585 women with paired samples have been included in the study. In the MS, 4% of the women are positive for hrHPV compared to 11% in the SS group. In 486/585 women, the results of the two samples are concordant. Among the non-concordant samples (13%), 62% were positive in SS and negative in MS. The opposite, negative in SS and positive in MS were seen in 4% of the samples. Among the MS negative samples, 32% were invalid in SS. Cytology was used as a triage test for HPV positive women, both for MS and SS. Of 23 hrHPV positive, 18 had normal cytology, 2 ASCUS, 1 LSIL and 1 HSIL. In the samples with abnormal cytology, 4/5 were hrHPV positive in both SS and MS. One sample was positive in SS but negative in MS.Discussion: In this age group, more women are hrHPV positive in SS compared to MS. This is in line with what other have seen. Among the very few hrHPV positive samples with abnormal cytology, the majority was hrHPV positive in both MS and SS. But since cytology is a poor triage marker in this age group clinical follow-up is needed before the effectiveness of the both sampling methods can be concluded.
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| 23. |
- Helenius, Gisela, 1973
(author)
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Tissue engineering in blood vessels
- 2005
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Doctoral thesis (other academic/artistic)abstract
- Severely occluded coronary- and peripheral arteries, caused by atherosclerotic plaques, are treated with bypass surgery. Autologous veins are the most commonly used replacement graft. Among the patients that need a vascular bypass, 5-10% lack appropriate replacement veins due to previous surgery of bad quality of the vessels. Available synthetic grafts fail due to high thrombogenicity and compliance mismatch. Considering the huge number of patients in need of a vascular bypass, there is a tremendous need for a replacement graft with similar properties to those of native blood vessels.The major aim of this thesis was to develop a tissue engineered blood vessel that can be used as a vascular graft in bypass surgery. The specific aims were to investigate the interactions between endothelial- and smooth muscle cells during static and dynamic conditions, the production of extracellular matrix proteins in a tissue engineered blood vessel and if bacterial cellulose has the potential to be used as a scaffold for tissue engineered blood vessels.Endothelial- and smooth muscle cells in co-culture affected each other and this interaction resulted in an altered expression of coagulation- and fibrinolytic factors. When the co-culture was exposed to shear stress, both endothelial- and smooth muscle cells responded to the stimulation, which also lead to an altered gene- and protein expression of coagulation- and fibrinolytic factors. These results are important to consider for tissue engineered blood vessels.Blood vessels engineered by combining human smooth muscle cells and a scaffold of poly (glycolic acid), produced qualitatively the same extracellular matrix proteins as native blood vessels, although quantitatively there were large differences. The results in this thesis show that it is feasible to construct a tissue engineered blood vessel in vitro.Bacterial cellulose was very well integrated into the host tissue and did not trigger any chronic inflammatory reactions. Thus, the biocompatible properties of bacterial cellulose make it a promising scaffold alternative for tissue engineered blood vessels.
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| 24. |
- Hermansson, Ruth S., et al.
(author)
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History of HPV in HPV-positive elderly women
- 2024
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In: European journal of obstetrics & gynecology and reproductive biology: X. - : Elsevier. - 2590-1613. ; 22
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Journal article (peer-reviewed)abstract
- BACKGROUND: The aim of this study was to examine the natural course of HPV infection in women of 60 years and older who were HPV positive at inclusion, and any association between HPV positivity in historical samples and dysplasia outcome. METHODS: Eighty-nine women aged 60-82 years, who tested positive for HPV between 2012 and 2016 were included. Sampling for cytology and/or histology was also performed. HPV genotyping was carried out on archived material back to 1999.RESULTS: Of the 89 HPV-positive women 16 had HSIL, 34 had LSIL and 39 were benign at inclusion. Of the women with HSIL, 50.0% had the same HPV type in the archive samples, 12.5% had another type, and 37.5% were HPV negative. Among the 34 women with LSIL, 47.1% had the same HPV type in archive samples, 5.8% had another type, and 47.1% were HPV negative. Of the 39 women without dysplasia at inclusion, 25.6% had the same HPV type in archive samples, 5.1% had another HPV type and 69.2% were HPV negative.CONCLUSION: Surprisingly few of the elderly women thus seem to have a history with the same or any HPV infection the years before being diagnosed with an HPV infection and dysplasia. The significance of an HPV infection for dysplasia development in elderly women is still not fully understood.
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| 25. |
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