| 41. |
- Rutegård, Martin, 1982-, et al.
(författare)
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Robotic low anterior resection with complete splenic flexure mobilization and defunctioning left-sided loop colostomy : a case series
- 2024
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Ingår i: Journal of Surgical Case Reports. - : Oxford University Press. - 2042-8812. ; 2024:1
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Tidskriftsartikel (refereegranskat)abstract
- A defunctioning stoma is used to alleviate the consequences of anastomotic leakage after low anterior resection for rectal cancer. A loop ileostomy is often preferred but may lead to dehydration and kidney injury. Here, we present a case series for an alternative: the left-sided loop colostomy. A convenience sample of four patients underwent robotic low anterior resection for rectal cancer. A complete splenic flexure mobilization and a total mesorectal excision were performed. To defunction the anastomosis, the redundant left colon was brought up to a stoma site in the left iliac fossa and matured as a loop colostomy. Two patients experienced minor stoma leaks and one also had a small prolapse, while all patients had their colostomies reversed on average 7 months after surgery without complications. There were no dehydration episodes and creatinine levels remained within baseline levels at end of follow-up (on average 18 months).
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| 42. |
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| 43. |
- Seibt, Henrik, et al.
(författare)
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Elevated levels of VCA0117 in response to external signals activates type VI secretion in Vibrio cholerae A1552
- 2020
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Ingår i: Environmental Microbiology. - : John Wiley & Sons. - 1462-2912 .- 1462-2920. ; 22:10, s. 4409-4423
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- The type VI nanomachine is critical for Vibrio cholerae to establish infections and to thrive in niches co‐occupied by competing bacteria. The genes for the type VI structural proteins are encoded in one large and two small auxiliary gene clusters. VCA0117 (VasH) – a σ54‐transcriptional activator – is strictly required for functionality of the type VI secretion system since it controls production of the structural protein Hcp. While some strains constitutively produce a functional system, others do not and require specific growth conditions of low temperature and high osmolarity for expression of the type VI machinery. Here, we trace integration of these regulatory signals to the promoter activity of the large gene cluster in which many components of the machinery and VCA0117 itself are encoded. Using in vivo and in vitro assays and variants of VCA0117, we show that activation of the σ54‐promoters of the auxiliary gene clusters by elevated VCA0117 levels are all that is required to overcome the need for specialized growth conditions. We propose a model in which signal integration via the large operon promoter directs otherwise restrictive levels of VCA0117 that ultimately dictates a sufficient supply of Hcp for completion of a functional type VI secretion system.
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| 44. |
- Severson, Tesa, et al.
(författare)
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Androgen receptor reprogramming demarcates prognostic, context-dependent gene sets in primary and metastatic prostate cancer
- 2022
-
Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The androgen receptor (AR) is a prostate master transcription factor. It binds to genetic enhancers, where it regulates gene activity and plays a fundamental role in prostate pathophysiology. Previous work has demonstrated that AR-DNA binding is systematically and consistently reprogrammed during prostate tumorigenesis and disease progression. We charted these reprogrammed AR sites and identified genes proximal to them. We were able to devise gene lists based on AR status within specific histological contexts: normal prostate epithelium, primary prostate tumor, and metastatic prostate cancer. We evaluated expression of the genes in these gene sets in subjects from two distinct clinical cohorts—men treated with surgery for localized prostate cancer and men with metastatic prostate cancer. Among men with localized prostate cancer, expression of genes proximal to AR sites lost in the transition from normal prostate to prostate tumor was associated with clinical outcome. Among men with metastatic disease, expression of genes proximal to AR sites gained in metastatic tumors was associated with clinical outcome. These results are consistent with the notion that AR is fundamental to both maintaining differentiation in normal prostate tissue and driving de-differentiation in advanced prostate cancer. More broadly, the study demonstrates the power of incorporating context-dependent epigenetic data into genetic analyses.
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| 45. |
- Sjöström, Martin, et al.
(författare)
-
A Combined Shotgun and Targeted Mass Spectrometry Strategy for Breast Cancer Biomarker Discovery
- 2015
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Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 14:7, s. 2807-2818
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Tidskriftsartikel (refereegranskat)abstract
- It is of highest importance to find proteins responsible for breast cancer dissemination, for use as biomarkers or treatment targets. We established and performed a combined nontargeted LC MS/MS and a targeted LC SRM workflow for discovery and validation of protein biomarkers. Eighty breast tumors, stratified for estrogen receptor status and development of distant recurrence (DR +/-), were collected. After enrichment of N-glycosylated peptides, label-free LC-MS/MS was performed on each individual tumor in triplicate. In total, 1515 glycopeptides from 778 proteins were identified and used to create a map of the breast cancer N-glycosylated proteome. Based on this specific proteome map, we constructed a 92-plex targeted label-free LC-SRM panel. These proteins were quantified across samples by LC SRM, resulting in 10 proteins consistently differentially regulated between DR+/DR- tumors. Five proteins were further validated in a separate cohort as prognostic biomarkers at the gene expression level. We also compared the LC-SRM results to clinically reported HER2 status, demonstrating its 'clinical accuracy. In conclusion, we demonstrate a combined mass spectrometry strategy, at large scale on clinical samples, leading to the identification and validation of five proteins as potential biomarkers for breast cancer recurrence. All MS data are available via ProteomeXchange and PASSEL with identifiers PXD001685 and PASS00643.
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| 46. |
- Sjöström, Martin, et al.
(författare)
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Clinicogenomic Radiotherapy Classifier Predicting the Need for Intensified Locoregional Treatment After Breast-Conserving Surgery for Early-Stage Breast Cancer.
- 2019
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Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 37:35, s. 3340-3349
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Tidskriftsartikel (refereegranskat)abstract
- Most patients with early-stage breast cancer are treated with adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) to prevent locoregional recurrence (LRR). However, no genomic tools are used currently to select the optimal RT strategy.We profiled the transcriptome of primary tumors on a clinical grade assay from the SweBCG91-RT trial, in which patients with node-negative breast cancer were randomly assigned to either whole-breast RT after BCS or no RT. We derived a new classifier, Adjuvant Radiotherapy Intensification Classifier (ARTIC), comprising 27 genes and patient age, in three publicly available cohorts, then independently validated ARTIC for LRR in 748 patients in SweBCG91-RT. We also compared previously published genomic signatures for ability to predict benefit from RT in SweBCG91-RT.ARTIC was highly prognostic for LRR in patients treated with RT (hazard ratio [HR], 3.4; 95% CI, 2.0 to 5.9; P < .001) and predictive of RT benefit (Pinteraction = .005). Patients with low ARTIC scores had a large benefit from RT (HR, 0.33 [95% CI, 0.21 to 0.52], P < .001; 10-year cumulative incidence of LRR, 6% v 21%), whereas those with high ARTIC scores benefited less from RT (HR, 0.73 [95% CI, 0.44 to 1.2], P = .23; 10-year cumulative incidence of LRR, 25% v 32%). In contrast, none of the eight previously published signatures were predictive of benefit from RT in SweBCG91-RT.ARTIC identified women with a substantial benefit from RT as well as women with a particularly elevated LRR risk in whom whole-breast RT was not sufficiently effective and, thus, in whom intensified treatment strategies such as tumor-bed boost, and possibly regional nodal RT, should be considered. To our knowledge, ARTIC is the first classifier validated as predictive of benefit from RT in a phase III clinical trial with patients randomly assigned to receive or not receive RT.
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| 47. |
- Sjöström, Martin, et al.
(författare)
-
Comprehensive transcriptomic profiling identifies breast cancer patients who may be spared adjuvant systemic therapy.
- 2020
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Ingår i: Clinical cancer research : an official journal of the American Association for Cancer Research. - 1078-0432. ; 26:1, s. 171-182
-
Tidskriftsartikel (refereegranskat)abstract
- There is currently no molecular signature in clinical use for adjuvant endocrine therapy omission in breast cancer. Given the unique trial design of SweBCG91-RT, where adjuvant endocrine and chemotherapy were largely unadministered, we sought to evaluate the potential of transcriptomic profiling for identifying patients who may be spared adjuvant endocrine therapy.We performed a whole transcriptome analysis of SweBCG91-RT, a randomized phase III trial of +/- radiotherapy after breast-conserving surgery for node-negative stage I-IIA breast cancer. 92% of patients were untreated by both adjuvant endocrine therapy and chemotherapy. We calculated 15 transcriptomic signatures from the literature and combined them into an Average Genomic Risk, which was further used to derive a novel 141-gene signature (MET141). All signatures were then independently examined in SweBCG91-RT, and in the publicly-available METABRIC cohort.In SweBCG91-RT, 454 patients were node-negative, post-menopausal and systemically untreated with ER-positive, HER2-negative cancers, which constitutes a low-risk subgroup and potential candidates for therapy omission. Most transcriptomic signatures were highly prognostic for distant metastasis, but considerable discordance was observed on the individual patient level. Within the MET141 low-risk subgroup (lowest 25th percentile of scores), 95% of patients were free of metastasis at 15 years even in the absence of adjuvant endocrine therapy. In a clinically low-risk subgroup of the METABRIC cohort not treated with systemic therapy, no breast cancer death occurred among the MET141 low-risk patients.Transcriptomic profiling identifies patients with an excellent outcome without any systemic adjuvant therapy in clinically low-risk patients of the SweBCG91-RT and METABRIC cohorts.
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| 48. |
- Sjöström, Martin, et al.
(författare)
-
Development and Validation of a Genomic Profile for the Omission of Local Adjuvant Radiation in Breast Cancer.
- 2023
-
Ingår i: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. - 1527-7755. ; 41:8, s. 1533-1540
-
Tidskriftsartikel (refereegranskat)abstract
- Adjuvant radiotherapy (RT) is used for women with early-stage invasive breast cancer treated with breast-conserving surgery. However, some women with low risk of recurrence may safely be spared RT. This study aimed to identify these women using a molecular-based approach.We analyzed two randomized trials of women with node-negative invasive breast cancer to ± RT following breast-conserving surgery: SweBCG91-RT (stage I-II, no adjuvant systemic therapy) and Princess Margaret (age 50 years or older, T1-T2, adjuvant tamoxifen). Transcriptome-wide profiling was performed (Affymetrix Human Exon 1.0 ST microarray). Patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative tumors and with gene expression data were included. The SweBCG91-RT cohort was divided into training (N = 243) and validation (N = 354) cohorts. A 16-gene signature named Profile for the Omission of Local Adjuvant Radiation (POLAR) was trained to predict locoregional recurrence (LRR) using elastic net regression. POLAR was then validated in the SweBCG91-RT validation cohort and the Princess Margaret cohort (N = 132).Patients categorized as POLAR low-risk without RT had a 10-year LRR of 6% (95% CI, 2 to 16) and 7% (0 to 27) in SweBCG91-RT and Princess Margaret cohorts, respectively. There was no significant benefit from RT in POLAR low-risk patients (hazard ratio [HR], 1.1 [0.39 to 3.4], P = .81, and HR, 1.5 [0.14 to 16], P = .74, respectively). Patients categorized as POLAR high-risk had a significant decreased risk of LRR with RT (HR, 0.43 [0.24 to 0.78], P = .0055, and HR, 0.25 [0.07 to 0.92], P = .038, respectively). An exploratory analysis testing for interaction between RT and POLAR in the combined validation cohort was performed (P = .066).The novel POLAR genomic signature on the basis of LRR biology may identify patients with a low risk of LRR despite not receiving RT, and thus may be candidates for RT omission.
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| 49. |
- Sjöström, Martin, et al.
(författare)
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Evaluation of MODIS gross primary productivity for Africa using eddy covariance data
- 2013
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Ingår i: Remote Sensing of Environment. - : Elsevier BV. - 0034-4257. ; 131, s. 275-286
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Tidskriftsartikel (refereegranskat)abstract
- MOD17A2 provides operational gross primary production (GPP) data globally at 1 km spatial resolution and 8-day temporal resolution. MOD17A2 estimates GPP according to the light use efficiency (LUE) concept assuming a fixed maximum rate of carbon assimilation per unit photosynthetically active radiation absorbed by the vegetation (epsilon(max)). Minimum temperature and vapor pressure deficit derived from meteorological data down-regulate epsilon(max) and constrain carbon assimilation. This data is useful for regional to global studies of the terrestrial carbon budget, climate change and natural resources. In this study we evaluated the MOD17A2 product and its driver data by using in situ measurements of meteorology and eddy covariance GPP for 12 African sites. MOD17A2 agreed well with eddy covariance GPP for wet sites. Overall, seasonality was well captured but MOD17A2 GPP was underestimated for the dry sites located in the Sahel region. Replacing the meteorological driver data derived from coarse resolution reanalysis data with tower measurements reduced MOD17A2 GPP uncertainties, however, the underestimations at the dry sites persisted. Inferred epsilon(max) calculated from tower data was higher than the epsilon(max) prescribed in MOD17A2. This, in addition to uncertainties in fraction of absorbed photosynthetically active radiation (FAPAR) explains some of the underestimations. The results suggest that improved quality of driver data, but primarily a readjustment of the parameters in the biome parameter look-up table (BPLUT) may be needed to better estimate GPP for African ecosystems in MOD17A2. (C) 2013 Elsevier Inc. All rights reserved.
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| 50. |
- Sjöström, Martin, et al.
(författare)
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Evaluation of satellite based indices for gross primary production estimates in a sparse savanna in the Sudan
- 2009
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Ingår i: Biogeosciences. - : Copernicus GmbH. - 1726-4189. ; 6:1, s. 129-138
-
Tidskriftsartikel (refereegranskat)abstract
- One of the more frequently applied methods for integrating controls on primary production through satellite data is the Light Use Efficiency (LUE) approach. Satellite indices such as the Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI) and the Shortwave Infrared Water Stress Index (SIWSI) have previously shown promise as predictors of primary production in several different environments. In this study, we evaluate NDVI, EVI and SIWSI derived from the Moderate Resolution Imaging Spectroradiometer (MODIS) satellite sensor against in-situ measurements from central Sudan in order to asses their applicability in LUE-based primary production modeling within a water limited environment. Results show a strong correlation between vegetation indices and gross primary production (GPP), demonstrating the significance of vegetation indices for deriving information on primary production with relatively high accuracy at similar areas. Evaluation of SIWSI however, reveal that the fraction of vegetation apparently is to low for the index to provide accurate information on canopy water content, indicating that the use of SIWSI as a predictor of water stress in satellite data-driven primary production modeling in similar semi-arid ecosystems is limited.
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