| 1. |
- Altai, Mohamed, et al.
(författare)
-
188Re-ZHER2:V2, a promising affibody-based targeting agent against HER2-expressing tumors : preclinical assessment
- 2014
-
Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 55:11, s. 8-1842
-
Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Affibody molecules are small (7 kDa) nonimmunoglobulin scaffold proteins with favorable tumor-targeting properties. Studies concerning the influence of chelators on biodistribution of (99m)Tc-labeled Affibody molecules demonstrated that the variant with a C-terminal glycyl-glycyl-glycyl-cysteine peptide-based chelator (designated ZHER2:V2) has the best biodistribution profile in vivo and the lowest renal retention of radioactivity. The aim of this study was to evaluate (188)Re-ZHER2:V2 as a potential candidate for radionuclide therapy of human epidermal growth factor receptor type 2 (HER2)-expressing tumors.METHODS: ZHER2:V2 was labeled with (188)Re using a gluconate-containing kit. Targeting of HER2-overexpressing SKOV-3 ovarian carcinoma xenografts in nude mice was studied for a dosimetry assessment.RESULTS: Binding of (188)Re-ZHER2:V2 to living SKOV-3 cells was demonstrated to be specific, with an affinity of 6.4 ± 0.4 pM. The biodistribution study showed a rapid blood clearance (1.4 ± 0.1 percentage injected activity per gram [%ID/g] at 1 h after injection). The tumor uptake was 14 ± 2, 12 ± 2, 5 ± 2, and 1.8 ± 0.5 %IA/g at 1, 4, 24, and 48 h after injection, respectively. The in vivo targeting of HER2-expressing xenografts was specific. Already at 4 h after injection, tumor uptake exceeded kidney uptake (2.1 ± 0.2 %IA/g). Scintillation-camera imaging showed that tumor xenografts were the only sites with prominent accumulation of radioactivity at 4 h after injection. Based on the biokinetics, a dosimetry evaluation for humans suggests that (188)Re-ZHER2:V2 would provide an absorbed dose to tumor of 79 Gy without exceeding absorbed doses of 23 Gy to kidneys and 2 Gy to bone marrow. This indicates that future human radiotherapy studies may be feasible.CONCLUSION: (188)Re-ZHER2:V2 can deliver high absorbed doses to tumors without exceeding kidney and bone marrow toxicity limits.
|
|
| 2. |
- Moberg, Christina, et al.
(författare)
-
De unga gör helt rätt när de stämmer staten
- 2022
-
Ingår i: Aftonbladet. - 1103-9000.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
|
|
| 3. |
- Olofsson, Sven-Erik, et al.
(författare)
-
Population-Based Study of Treatment Guided by Tumor Marker Decline in Patients With Metastatic Nonseminomatous Germ Cell Tumor : A Report From the Swedish-Norwegian Testicular Cancer Group
- 2011
-
Ingår i: Journal of Clinical Oncology. - 0732-183X .- 1527-7755. ; 29:15, s. 2032-2039
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose From 1995 to 2003, 603 adult patients from Sweden and Norway with metastatic testicular nonseminomatous germ cell tumor (NSGCT) were included prospectively in a population-based protocol with strict guidelines for staging, treatment, and follow-up. Patients with extragonadal primary tumor or previous treatment for contralateral testicular tumor were excluded. The basic strategy was to individualize treatment according to initial tumor marker response. Methods Initial treatment for all patients was two courses of standard bleomycin, etoposide, and cisplatin (BEP), with tumor markers analyzed weekly. Good response was defined as a half-life (t(1/2)) for alpha-fetoprotein (AFP) of <= 7 days and/or for beta-human chorionic gonadotropin (beta-HCG) of <= 3 days. Patients with prolonged marker t(1/2) (ie, poor response) received intensification with addition of ifosfamide (BEP-if/PEI) in step 1. If poor response continued, the treatment was intensified with high-dose chemotherapy with stem-cell rescue as step 2. Results Overall, 99% of all patients with metastatic testicular NSGCT in the population were included in the protocol. Median follow-up was 8.2 years. Seventy-seven percent of the patients were treated with BEP alone; 18% received intensification step 1%, and 5% received intensification step 2. Grouped according to International Germ Cell Consensus Classification, 10-year overall survival was 94.7% in good-prognosis patients, 90.0% in intermediate-prognosis patients, and 67.4% in poor-prognosis patients. Conclusion With detailed treatment protocols and a dedicated collaborative group of specialists, treatment results comparable to those reported from large single institutions can be achieved at national level. With the treatment principles used in Swedish-Norwegian Testicular Cancer Group study SWENOTECA IV, the survival of intermediate-prognosis patients is remarkable and close to that of good-prognosis patients.
|
|
| 4. |
|
|
| 5. |
- Saarela, Svetlana, et al.
(författare)
-
Comparing frameworks for biomass prediction for the Global Ecosystem Dynamics Investigation
- 2022
-
Ingår i: Remote Sensing of Environment. - : Elsevier. - 0034-4257 .- 1879-0704. ; 278
-
Tidskriftsartikel (refereegranskat)abstract
- NASA's Global Ecosystem Dynamics Investigation (GEDI) mission offers data for temperate and pan-tropical estimates of aboveground forest biomass (AGB). The spaceborne, full-waveform LiDAR from GEDI provides sample footprints of canopy structure, expected to cover about 4% of the land area following two years of operation. Several options are available for estimating AGB at different geographical scales. Using GEDI sample data alone, gridded biomass predictions are based on hybrid inference which correctly propagates errors due to the modeling and accounts for sampling variability, but this method requires at least two GEDI tracks in the area of interest. However, there are significant gaps in GEDI coverage and in some areas of interest GEDI data may need to be combined with other wall-to-wall remotely sensed (RS) data, such as those from multispectral or SAR sensors. In these cases, we may employ hierarchical model-based (HMB) inference that correctly considers the additional model errors that result from relating GEDI data to the wall-to-wall data. Where predictions are possible from both hybrid and HMB inference the question arises which framework to choose, and under what circumstances? In this paper, we make progress towards answering these questions by comparing the performance of the two prediction frameworks under conditions relevant for the GEDI mission. Conventional model-based (MB) inference with wall-to-wall TanDEM-X data was applied as a baseline prediction framework, which does not involve GEDI data at all. An important feature of the study was the comparison of AGB predictors in terms of both standard deviation (SD: the square root of variance) and root mean square error (RMSE: the square root of mean square error – MSE). Since, in model-based inference, the true AGB in an area of interest is a random variable, comparisons of the performance of prediction frameworks should preferably be made in terms of their RMSEs. However, in practice only the SD can be estimated based on empirical survey data, and thus it is important also to study whether or not the difference between the two uncertainty measures is small or large under conditions relevant for the GEDI mission. Our main findings were that: (i) hybrid and HMB prediction typically resulted in smaller RMSEs than conventional MB prediction although the difference between the three frameworks in terms of SD often was small; (ii) in most cases the difference between hybrid and HMB inference was small in terms of both RMSE and SD; (iii) the RMSEs for all frameworks was substantially larger than the SDs in small study areas whereas the two uncertainty measures were similar in large study areas, and; (iv) spatial autocorrelation of model residual errors had a large effect on the RMSEs of AGB predictors, especially in small study areas. We conclude that hybrid inference is suitable in most GEDI applications for AGB assessment, due to its simplicity compared to HMB inference. However, where GEDI data are sparse HMB inference should be preferred.
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Asp, Michaela, et al.
(författare)
-
A Spatiotemporal Organ-Wide Gene Expression and Cell Atlas of the Developing Human Heart
- 2019
-
Ingår i: Cell. - : CELL PRESS. - 0092-8674 .- 1097-4172. ; 179:7, s. 1647-
-
Tidskriftsartikel (refereegranskat)abstract
- The process of cardiac morphogenesis in humans is incompletely understood. Its full characterization requires a deep exploration of the organ-wide orchestration of gene expression with a single-cell spatial resolution. Here, we present a molecular approach that reveals the comprehensive transcriptional landscape of cell types populating the embryonic heart at three developmental stages and that maps cell-type-specific gene expression to specific anatomical domains. Spatial transcriptomics identified unique gene profiles that correspond to distinct anatomical regions in each developmental stage. Human embryonic cardiac cell types identified by single-cell RNA sequencing confirmed and enriched the spatial annotation of embryonic cardiac gene expression. In situ sequencing was then used to refine these results and create a spatial subcellular map for the three developmental phases. Finally, we generated a publicly available web resource of the human developing heart to facilitate future studies on human cardiogenesis.
|
|
| 9. |
- Asp, Michaela, et al.
(författare)
-
An organ‐wide gene expression atlas of the developing human heart
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- The human developing heart holds a greater proportion of stem-cell-like cells than the adult heart. However, it is not completely understood how these stem cells differentiate into various cardiac cell types. We have performed an organ-wide transcriptional landscape analysis of the developing heart to advance our understanding of cardiac morphogenesis in humans. Comprehensive spatial gene expression analyses identified distinct profiles that correspond not only to individual chamber compartments, but also distinctive regions within the outflow tract. Furthermore, the generated spatial expression reference maps facilitated the assignment of 3,787 human embryonic cardiac cells obtained from single-cell RNA-sequencing to an in situlocation. Through this approach we reveal that the outflow tract contains a wider range of cell types than the chambers, and that the epicardium expression profile can be traced to several cell types that are activated at different stages of development. We also provide a 3D spatial model of human embryonic cardiac cells to enable further studies of the developing human heart.
|
|
| 10. |
- Asp, Michaela, et al.
(författare)
-
Spatial Isoform Profiling within Individual Tissue Sections
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Spatial Transcriptomics has been shown to be a persuasive RNA sequencingtechnology for analyzing cellular heterogeneity within tissue sections. Thetechnology efficiently captures and barcodes 3’ tags of all polyadenylatedtranscripts from a tissue section, and thus provides a powerful platform whenperforming quantitative spatial gene expression studies. However, the currentprotocol does not recover the full-length information of transcripts, andconsequently lack information regarding alternative splice variants. Here, weintroduce a novel protocol for spatial isoform profiling, using SpatialTranscriptomics barcoded arrays.
|
|
