1. |
|
|
2. |
|
|
3. |
- Bekele, Maheteme, et al.
(author)
-
Tumor and immune cell profiling in breast cancer using highly multiplexed imaging mass cytometry single-cell technology demonstrates tumor heterogeneity and immune phenotypic abnormality in Ethiopian women
- 2020
-
In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 80:21 Suppl.
-
Journal article (other academic/artistic)abstract
- Background: Tumor heterogeneity represents a complex challenge to cancer treatment, disease recurrence, and patient survival. Imaging mass cytometry (IMC) is an emerging proteomic tool for cancer profiling in tumor tissue samples. IMC enables digital image analysis by multiplexed immunostaining of cells and proteins within tissue and preserves spatial relations within tumor environment. We have applied IMC based approach to study the heterogeneity of invasive breast carcinoma protein expression pattern in formalin fixed paraffin embedded tissues.Methods: A total of 10 region of interest (ROI) derived from 5 patients with primary invasive breast carcinoma representing three molecular subclasses (HR+/HER2-,HER2+/HR- and TNBC) were stained with a 30-marker IMC metal labeled antibody panel (α-SMA, EGFR, p53, CD33, CD16, CD163, CD11b, PDL1, CD31, CD45, D44,Vimentin, FoxP3, CD4, ECadherin, CD68, CD20, CD8a, Cytokeratin7, PD1, GranzymeB, Ki67, ColTypeI, CD3, CD45RO, HLADR, DARC & CD11c). Tissue imaging was done by quantifying the abundance of bound antibody with a Hyperion IMC. MCD Viewer was used for visualization purpose and to export raw 16-bit tiff images for segmentation on CellProfiler. Segmentation masks were combined with the individual tiff files to extract single-cell information from each individual image. HistoCAT was applied to perform unbiased clustering of cell populations using the PhenoGraph algorithm and clustered cell populations was overlaid on t-SNE plot. The relative marker expression was used to generate heat-maps and each cluster was manually assigned a phenotype based on its expression profile.Results: The t-SNE generated from each ROI revealed different distinct cell populations and we report the presence of diverse tumor and immune cell populations in our samples. The (min, max) number of PhenoGraph clustered tumor cell populations in HR+/HER2-, HER2+ and TNBC Cases were (5,8) (7,9) and (5,7) respectively. Similarly, the (min, max) number of PhenoGraph clustered immune cell populations in HR+/HER2-, HER2+ and TNBC Cases were (5,8) (7,9) and (5,7) respectively. We also document the presence of inter and intra-tumor heterogeniety in expression of PD1 and PDL1 in all the tumor subtypes studied. Additionally, we report a phenotypic abnormality in the immune cell populations identified with dual or triple markers expression of the canonical CD antigens of T-Cells, B-Cells and macrophages.Conclusion: The current study demonstrates high-dimensional visualization with the simultaneous analysis of epithelial, immune, and stromal components using IMC can be used to explore cell populations in tumor tissue to quantify tumor heterogeneity or identification of novel clustering patterns that has potential for translational research and clinical practice. Significance: This study presents the potential of Imaging Mass Cytometry and single cell analysis algorithms in multiplex high throughput tumor tissue studies.
|
|
4. |
|
|
5. |
-
En båge genom tiden - ritualer kring en göteborgshistoria. Om Flickläroverket i Artisten
- 2024
-
Editorial collection (other academic/artistic)abstract
- 1929 bildades Göteborgs första Högre allmänna läroverk för Flickor – Flickläroverket som fick en byggnad 1935 i det kulturella centrumet, Götaplatsen. Efter några år som Kjellbergska gymnasiet, sedan Komvux, blev byggnaden del av Artisten, Högskolan för scen och musik, HSM 1992. Byggnaden har burit kvinnors utbildning, konst och kultur över många generationer, en minneskedja som nu är bruten. Boken - En båge genom tiden – ritualer kring en göteborgshistoria – en konst- och forskningsantologi – är resultatet av de offentliga minnesdagar där de deltagande drygt 200 kvinnorna (70– 97 år) som varit elever på Flickläroverket, studenter vid Artisten, konstnärer och forskare – bidrog till och deltog i gestaltande ritualer, minnesrum, dans, utställningar och samtal som gav liv åt en utbildningskultur och konst som berört samhället i generationer. I boken bidrar ett 20-tal Göteborgsbaserade konstnärer och forskare med olika perspektiv på byggnadens poetiska, sociala och konstnärliga dimensioner. Bland annat beskrivs återskapandet av Bågdansen, som dansades varje år vid Lucia mellan 1934-1972. Här beskrivs även den medie-debatt som ledde till räddningen av målningen Dansen av Nils Nilsson från 1935 och hur nedtagningen gick till. Tillsammans med ett rikt foto- och bildmaterial, filmdokumentationer och ett ljudarkiv utgör boken ett tidsdokument där konst fungerar som minnesbärare över tid och rum.
|
|
6. |
- Gebregzabher, Endale, et al.
(author)
-
Detection of High- and Low-Risk HPV DNA in Archived Breast Carcinoma Tissues from Ethiopian Women
- 2021
-
In: International Journal of Breast Cancer. - : Hindawi Publishing Corporation. - 2090-3170 .- 2090-3189. ; 2021
-
Journal article (peer-reviewed)abstract
- Background: Human papilloma virus (HPV) is involved in the development of cancer of the cervix, mouth and throat, anus, penis, vulva, or vagina, but it has not been much considered as a cause of breast cancer. Recently, a number of investigations have linked breast cancer to viral infections. High-risk HPV types, predominantly HPV types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, and 59, are established as carcinogens in humans. In this study we aimed to detect 19 high-risk and 9 low-risk HPVs from archived breast tumor tissue among Ethiopian women.Methods: In this study, 75 breast cancer patients from Tikur Anbassa Specialized Hospital in Addis Ababa (Ethiopia) were included. HPV detection and genotyping were done using the novel Anyplex™ II HPV28 Detection Assay at the Orebro University Hospital, Sweden. The Anyplex™ II PCR System detects 19 high-risk HPV types (16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 69, 73, and 82) and 9 low-risk HPV types (6, 11, 40, 42, 43, 44, 54, 61, and 70). IHC for p16 was done using an automated system, the Dako Autostainer Link.Results: Out of the 75 valid tests, two were found to be positive (2.7%) for HPV. One of the cases was positive for the high-risk HPV16 genotype while the other was positive both for the high-risk HPV39 and the low-risk HPV6. The cell cycle protein p16 was highly expressed in the case positive for the high-risk HPV16, but it was not expressed in the case positive for HPV39.Conclusion: The prevalence of HPV is low in Ethiopian breast cancer patients, but the role played by HPV in breast carcinogenesis among Ethiopian breast cancer patients cannot be commented based on these observations.
|
|
7. |
- Hadgu, Endale, et al.
(author)
-
Distribution and characteristics of androgen receptor (AR) in breast cancer among women in Addis Ababa, Ethiopia : A cross sectional study
- 2020
-
In: PLOS ONE. - : Public Library Science. - 1932-6203. ; 15:5
-
Journal article (peer-reviewed)abstract
- Evaluation of the role of androgen receptor (AR) in the biology of breast cancer is an emerging area of research. There are compelling evidences that AR expression may be used to further refine breast cancer molecular subtyping with prognostic and therapeutic implications. Many studies indicated co-expression of AR with the hormonal receptors in breast cancer has a favorable prognosis. AR is also investigated by many researchers as a potential therapeutic target in treatment of breast cancer. Studies on the frequency and distribution of AR in breast cancer among Africans is barely available. Given the heightened interest to understand its role in breast cancer, we determined AR expression and assessed its association with clinicopathological parameters among Ethiopian women. In this study, 112 newly diagnosed patient with invasive breast cancer at Tikur Anbessa Specialized Hospital were enrolled. Immunohistochemical assessment of AR, ER, PR, Ki67 and HER2 were performed using tissue microarrays (TMA) constructed from their primary tumor block. Out of the 112 participants, 91 (81%) were positive for AR expression and the remaining 21 participants (19%) were negative for AR expression. Expression of AR in ER+, HER2+ and TNBC cases were 93%, 83% and 48% respectively. Our study reveals AR is expressed in a significant number of breast cancers patients and this may indicate that breast cancers cases in Ethiopia have favorable prognosis and could benefit from progresses in AR targeted treatments. Since AR expression has important consequences on the prognosis and treatment of breast cancer, further studies with an increased number of participants is necessary to confirm our reports.
|
|
8. |
- Padma, Arvind M., et al.
(author)
-
Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning
- 2021
-
In: Npj Regenerative Medicine. - : Springer Science and Business Media LLC. - 2057-3995. ; 6:1
-
Journal article (peer-reviewed)abstract
- Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellularized constructs derived from decellularized tissue restored fertility in rodent models and mandate translational studies. In this study, we decellularized whole sheep uterus with three different protocols using 0.5% sodium dodecyl sulfate, 2% sodium deoxycholate (SDC) or 2% SDC, and 1% Triton X-100. Scaffolds were then assessed for bioactivity using the dorsal root ganglion and chorioallantoic membrane assays, and we found that all the uterus scaffolds exhibited growth factor activity that promoted neurogenesis and angiogenesis. Extensive recellularization optimization was conducted using multipotent sheep fetal stem cells and we report results from the following three in vitro conditions; (a) standard cell culturing conditions, (b) constructs cultured in transwells, and (c) scaffolds preconditioned with matrix metalloproteinase 2 and 9. The recellularization efficiency was improved short-term when transwells were used compared with standard culturing conditions. However, the recellularization efficiency in scaffolds preconditioned with matrix metalloproteinases was 200-300% better than the other strategies evaluated herein, independent of decellularization protocol. Hence, a major recellularization hurdle has been overcome with the improved recellularization strategies and in vitro platforms described herein. These results are an important milestone and should facilitate the production of large bioengineered grafts suitable for future in vivo applications in the sheep, which is an essential step before considering these principles in a clinical setting.
|
|
9. |
- Abrantes, João A., et al.
(author)
-
Relationship between factor VIII activity, bleeds and individual characteristics in severe hemophilia A patients
- 2020
-
In: Haematologica. - : Ferrata Storti Foundation. - 0390-6078 .- 1592-8721. ; 105:5, s. 1443-1453
-
Journal article (peer-reviewed)abstract
- Pharmacokinetic-based prophylaxis of replacement factor VIII products has been encouraged in the past years, but the exposure (factor VIII activity)-response (bleeding frequency) relationship remains unclear. The aim of this study was to characterize the relationship between factor VIII dose, plasma factor VIII activity, bleeding patterns and individual characteristics in severe hemophilia A patients. Pooled pharmacokinetic and bleeding data during prophylactic treatment with BAY 81-8973 (octocog alfa) were obtained from the three LEOPOLD trials. The population pharmacokinetics of factor VIII activity and longitudinal bleeding frequency, as well as bleeding severity, were described using nonlinear mixed effects modelling in NONMEM. In total, 183 patients (median age 22 years [range, 1-61]; weight 60 kg [11-124]) contributed with 1535 plasma factor VIII activity observations, 633 bleeds and 11 patient/study characteristics (median observation period 12 months [3.1-13.1]). A parametric repeated time-to-categorical bleed model, guided by plasma factor VIII activity from a 2-compartment population pharmacokinetic model, described the time to the occurrence of bleeds and their severity. Bleeding probability decreased with time of study, and a bleed was not found to affect the time of the next bleed. Several covariate effects were identified, including the bleeding history in the 12-month pre-study period increasing the bleeding hazard. However, unexplained inter-patient variability for the phenotypic bleeding pattern remained large (111%CV). Further studies to translate the model into a tool for dose individualization that considers the individual bleeding risk are required. Research based on a post-hoc analysis of the LEOPOLD studies (ClinicalTrials.gov identifiers NCT01029340, NCT01233258 and NCT01311648).
|
|
10. |
- af Hällström, Anna, 1987, et al.
(author)
-
The role of social ties in collaborative project networks: A tale of two construction cases
- 2021
-
In: Construction Management and Economics. - : Informa UK Limited. - 1466-433X .- 0144-6193. ; 39:9, s. 723-738
-
Journal article (peer-reviewed)abstract
- Collaborative project delivery models (CPDMs) are increasing in popularity as infrastructure con-struction projects become more complex and grow in scale and scope. CPDMs build on highlevels of trust, information exchange and formal contractual relations, creating complex relation-ships between actors in the project network. The literature emphasizes the procurement phaseand contractual aspects of CPDMs; however, few studies explicitly focus on the role of socialrelationships in CPDM projects. Social network theory has recently been introduced in the archi-tecture, engineering and construction industry industry to study relationships between networkactors, but the role of social ties within CPDM project networks is still unclear. Through twoqualitative case studies, we have analyzed the role of social ties in projects applying a CPDMcontract. The empirical evidence of 41 semi-structured interviews and observations points toaspects that affect the development of social ties in CPDMs, such as initial project setup, projectidentification, perception of actors, resource sharing and shared space, as well as the importanceof formal and informal ties for supporting collaborative project practices. The evidence showshow social ties develop into negative or positive bonds affecting the level of collaboration. Thisstudy contributes by emphasizing the interplay between project networks using CPDMs andsocial ties.
|
|