| 1. |
- Gustafsson, Anna, et al.
(författare)
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Gas6 and the receptor tyrosine kinase Axl in clear cell renal cell carcinoma.
- 2009
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 4:10, s. e7575-
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The molecular biology of renal cell carcinoma (RCC) is complex and not fully understood. We have recently found that the expression of the receptor tyrosine kinase Axl in the RCC tumors independently correlates with survival of the patients. PRINCIPAL FINDINGS: Here, we have investigated the role of Axl and its ligand Gas6, the vitamin-K dependent protein product of the growth arrest-specific gene 6, in clear cell RCC (ccRCC) derived cells. The Axl protein was highly expressed in ccRCC cells deficient in functional von Hippel-Lindau (VHL) protein, a tumor suppressor gene often inactivated in ccRCC. VHL reconstituted cells expressed decreased levels of Axl protein, but not Axl mRNA, suggesting VHL to regulate Axl expression. Gas6-mediated activation of Axl in ccRCC cells resulted in Axl phosphorylation, receptor down-regulation, decreased cell-viability and migratory capacity. No effects of the Gas6/Axl system could be detected on invasion. Moreover, in ccRCC tumor tissues, Axl was phosphorylated and Gas6 gamma-carboxylated, suggesting these molecules to be active in vivo. SIGNIFICANCE: These results provide novel information regarding the complex function of the Gas6/Axl system in ccRCC.
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| 2. |
- Lindgren, David, et al.
(författare)
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Isolation and characterization of progenitor-like cells from human renal proximal tubules.
- 2011
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Ingår i: American Journal of Pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 178:2, s. 828-837
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Tidskriftsartikel (refereegranskat)abstract
- The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDH(high) and ALDH(low) cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population scattered through the proximal tubules (PTs). These cells expressed CD24 and CD133, previously described markers for renal progenitors of Bowman's capsule. Furthermore, we show that the PT cells, and the glomerular progenitors, are positive for KRT7, KRT19, BCL2, and vimentin. In addition, tubular epithelium regenerating on acute tubular necrosis displayed long stretches of CD133(+)/VIM(+) cells, further substantiating that these cells may represent a progenitor cell population. Furthermore, a potential association of these progenitor cells with papillary renal cell carcinoma was discovered. Taken together, our data demonstrate the presence of a previously unappreciated subset of the PT cells that may be endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules.
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| 3. |
- Boström, Anna-Karin, et al.
(författare)
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Effects of TGF-β signaling in Clear Cell Renal Cell Carcinoma cells.
- 2013
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Ingår i: Biochemical and Biophysical Research Communications. - : Elsevier BV. - 1090-2104 .- 0006-291X. ; 435:1, s. 126-133
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Tidskriftsartikel (refereegranskat)abstract
- Clear cell renal cell carcinoma (ccRCC) is by far the most common type of kidney cancer and is characterized by loss of the tumor suppressor gene von Hippel-Lindau (VHL). ccRCC patients with metastatic disease has poor prognosis and today's therapy is insufficient. The cytokine Transforming Growth Factor-β (TGF-β) has been extensively studied in tumor biology and is believed to serve a variety of functions in tumor progression. We have previously shown that inhibition of NOTCH signaling causes a reduced migratory and invasive capacity of ccRCC cells, at least partly by a cross-talk with the TGF-β pathway. In the present study we aimed to further clarify the role of TGF-β signaling in ccRCC. We investigated the effects of TGF-β pathway modulation and showed that TGF-β inhibition attenuates the invasive capacity of ccRCC cells. By performing expression profiling we obtained a gene signature of the TGF-β induced response in ccRCC cells. The expression analyses revealed an extensive overlap between the TGF-β response and genes regulated by the hypoxia inducible factor (HIF). The link between the hypoxic and the TGF-β pathways was further corroborated by functional experiments, which demonstrated that TGF-β pathway activity was attenuated upon reintroduction of functional VHL in ccRCC.
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| 4. |
- Boström, Anna-Karin, et al.
(författare)
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Sarcomatoid conversion of clear cell renal cell carcinoma in relation to epithelial-to-mesenchymal transition.
- 2012
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Ingår i: Human Pathology. - : Elsevier BV. - 1532-8392 .- 0046-8177. ; 43, s. 708-719
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Tidskriftsartikel (refereegranskat)abstract
- Approximately 8% of clear cell renal cell carcinoma cases contain regions of radically different morphology, demonstrating a mesenchymal appearance histologically resembling sarcomas. These biphasic neoplasms are called sarcomatoid clear cell renal cell carcinoma. Patients diagnosed with sarcomatoid clear cell renal cell carcinoma face a considerably worse prognosis due to an increased propensity for metastasis. In the present study we investigate whether the sarcomatoid conversion of clear cell renal cell carcinoma could be interpreted as linked to the process of epithelial-mesenchymal transition. Using 6 biphasic clear cell renal cell carcinoma cases we show that sarcomatoid clear cell renal cell carcinoma shares characteristic markers associated with loss of von Hippel-Lindau tumor suppressor with conventional clear cell renal cell carcinoma and also exhibits a markedly higher proliferative index. Furthermore the sarcomatoid elements demonstrate an enhanced expression of epithelial-mesenchymal transition related mesenchymal markers as compared with the clear cell renal cell carcinoma counterparts. We further selected a representative case, clinically demonstrating direct overgrowth of the sarcomatoid component into the liver and colon, for extended immunohistochemical characterization, resulting in a further set of positive and negative epithelial-mesenchymal transition markers as well as pronounced transforming growth factor β positivity, indicating that sarcomatoid clear cell renal cell carcinoma may be associated to epithelial-mesenchymal transition. Transforming growth factor β1 exposure of in vitro cultured primary clear cell renal cell carcinoma cells resulted in cells adopting a mesenchymal morphology similar to sarcomatoid clear cell renal cell carcinoma. Corresponding changes in RNA levels for key epithelial-mesenchymal transition markers were also seen. We therefore suggest that sarcomatoid clear cell renal cell carcinoma morphologically and immunohistochemically may represent a completed epithelial-mesenchymal transition and that transforming growth factor β1 could be an important driving force during the sarcomatoid transdifferentiation of clear cell renal cell carcinoma.
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| 5. |
- Boström, Anna-Karin
(författare)
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TGF-B signaling in Neuroblastoma and Renal Cell Carcinoma
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The tubular cells of the adult kidney are normally mitotically quiescent, in stark contrast to the massive regenerative capacity of the injured renal epithelium. In Paper I we characterized a new cell population of progenitor cells using ALDH as a selection marker. These cells are situated in the proximal tubular epithelium and are called proximal tubular progenitor cells (PTPCs). Gene expression analysis of the PTPCs together with functional and immunohistochemical studies revealed that these cells might be responsible for the regeneration of damaged tubular epithelium. Clear cell RCC (ccRCC) is the most common type of RCC and is characterized by loss of function of the tumor suppressor gene von Hippel-Lindau (VHL). In Paper II and III we investigated the role of Notch and TGF-β signaling in ccRCC. Here we reported a cross talk between the two pathways and demonstrated a correlation between elevated TGF-β activity and worse prognosis in ccRCC patients. This correlation, in corroboration with functional migration and proliferation data, suggested that ccRCC cells have escaped the cytostatic effects of TGF-β signaling and that TGF-β instead increases the metastatic potential of ccRCCs. Sarcomatoid areas can occasionally be found in all types of renal malignancies and patients displaying sarcomatoid features have a very poor prognosis. In Paper IV we analyzed six ccRCC cases with sarcomatoid areas and show that sarcomatoid RCC demonstrate an enhanced expression of epithelial-to-mesenchymal transition (EMT)-related markers as compared to the ccRCC counterparts and that TGF-β might be the driving force behind this process. Neuroblastoma (NB) is a tumor arising the sympathetic nervous system in children and high-risk NBs are characterized by increased MYC-N/MYC activity. In Paper V we examined the protein response upon activation of the micro-RNA cluster miR-17-92 in NB using quantitative mass spectrometry. We showed that activation of the miR-17-92 cluster affected multiple oncogenic pathways including key effectors of the TGF-β signaling cascade. We report a connection between elevated expression of miR-17-92, low TGF-β signaling, and decreased patient survival.
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| 6. |
- Boström, Elisabeth Almer, 1983, et al.
(författare)
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Resistin and insulin/insulin-like growth factor signaling in rheumatoid arthritis.
- 2011
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Ingår i: Arthritis and rheumatism. - : Wiley. - 1529-0131 .- 0004-3591. ; 63:10, s. 2894-904
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Tidskriftsartikel (refereegranskat)abstract
- Human resistin has proinflammatory properties that activate NF-κB-dependent pathways, whereas its murine counterpart is associated with insulin resistance. The aim of this study was to examine potential cross-talk between resistin and insulin/insulin-like growth factor (IGF) signaling in rheumatoid arthritis (RA).
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| 7. |
- Boström, Kristina Bengtsson, et al.
(författare)
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Primary care physicians' concerned voices on sickness certification after a period of reorganization. Focus group interviews in Sweden
- 2020
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Ingår i: Scandinavian Journal of Primary Health Care. - : Informa UK Limited. - 0281-3432 .- 1502-7724. ; 38:2, s. 146-155
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This study explored the views of primary health care (PHC) physicians on sickness certification after reforms in 2005 prompted by the Swedish government to increase the quality and decrease the inequalities, and costs of sickness certification. Design: Qualitative design with focus group interviews. Data were analysed using qualitative content analysis. Setting: Urban and rural PHC centres in Region Vastra Gotaland, Sweden. Subjects: GPs, interns, GP trainees and locums working in PHC centres 2015. Six focus group interviews with 28 physicians were performed. Main outcome measures: Experiences and reflections about the sickness certification system. Results: The latent content was formulated in a theme: 'The physicians perceived the sickness certification process as emotive and a challenge to master with differing demands and expectations from authorities, management and patients'. Sickness certification could be easy in clear-cut situations or difficult when other factors besides the pure medical were ruling the decisions. The physicians' coping strategies for the task included both active measures (cooperation with health care staff and social insurance officers) and passive adaptation (giving in or not caring too much) to the circumstances. Proposals for the future were to transfer lengthy sickness certifications and rehabilitation to specialized teams and increase cooperation with rehabilitation coordinators and social insurance officers. Conclusions: Political decisions on laws and regulations for sickness certification impacted the primary health care making the physicians' work difficult and burdensome. Their views and suggestions should be carefully considered in future organization of primary care.
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| 8. |
- Frisendahl, Nathalie, et al.
(författare)
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Can the 1-Leg Standing Test Be Replaced by Self-reported Balance in the First-Time Injurious Fall Screening Tool?
- 2023
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Ingår i: Journal of Geriatric Physical Therapy. - : Lippincott Williams & Wilkins. - 1539-8412 .- 2152-0895. ; 46:2, s. 103-109
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Tidskriftsartikel (refereegranskat)abstract
- Background and Purpose: The First-time Injurious Fall (FIF) screening tool was created to identify fall risk in community-living older men and women, who may be targets for primary preventive interventions. The FIF tool consists of 3 self-reported questions and 1 physical test (1-leg standing balance). The purpose of this study was to examine the predictive ability of the FIF tool and a modified FIF tool (in which 1-leg standing is replaced by self-reported balance) for first-time injurious falls.Methods: A cohort of 1194 community-living people 60 years and older from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K), Sweden, was followed longitudinally for 5 years. Data on injurious falls were collected from registered data and were defined as receipt of care after a fall. The predictive ability of the FIF tool and the m-FIF tool was explored using Harrell's C statistic, stratified by sex.Results and Discussion: The injurious fall rate per 1000 person-years was 54.9 (95% CI: 47.22-63.78) for women and 36.3 (95% CI: 28.84-45.78) for men. The predictive ability for women and men according to Harrell's C statistic was 0.70 and 0.71 for the FIF tool and the m-FIF tool. The predictive ability was 0.70 and 0.69 for 1-leg standing, and 0.65 and 0.60 for self-reported balance problems.Conclusions: The m-FIF tool presented similar predictive ability as the FIF tool regarding first-time injurious falls. This finding could extend the usefulness of the tool to other settings, such as to electronic health (eHealth). A quickly and easily administered screening tool can help physical therapists to identify people with a high risk of falling who may need to undergo a more comprehensive fall risk assessment.
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| 9. |
- Frisendahl, Nathalie, et al.
(författare)
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Predictive Performance of the FIF Screening Tool in 2 Cohorts of Community-Living Older Adults
- 2020
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Ingår i: Journal of the American Medical Directors Association. - : Elsevier. - 1525-8610 .- 1538-9375. ; 21:12, s. 1900-1905
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The First-time Injurious Fall (FIF) screening tool was created to identify fall risk in communityliving older adults who may benefit from primary preventive interventions. The aim of this study was to evaluate the predictive performance of the FIF tool in 2 cohorts of older adults. Design: Longitudinal cohort study. Setting and Participants: The Swedish National Study on Aging and Care in Skane (SNAC-S) and Blekinge (SNAC-B), Sweden. Community-living people aged >= 60 years (n = 2766). Methods: Nurses and physicians collected data in the 2 cohorts through interviews and testing. Data on injurious falls were collected from register data and were defined as receipt of care after a fall. The FIF tool, consisting of 3 questions and 1 balance test, was examined in relation to injurious falls for up to 5 years of follow-up using Cox proportional hazards models. The predictive performance of the FIF tool was further explored using Harrell C statistic and Youden cut-off for sensitivity and specificity. Results: The hazard ratios (HRs) of an injurious fall in the high-risk group for women and men were 3.80 (95% confidence interval [CI] 2.53, 5.73) and 5.10 (95% CI 2.57, 10.12) in SNAC-S and 4.45 (95% CI 1.86, 10.61) and 32.58 (95% CI 4.30, 247.05) in SNAC-B compared with those in the low risk group. The sensitivity and specificity of the Youden cut-off point (3 or higher for high-risk) were 0.64 and 0.69 for women and 0.68 and 0.69 for men in SNAC-S, and 0.64 and 0.74 for women and 0.94 and 0.68 for men in SNAC-B. The predictive values (Harrell C statistic) for the scores for women and men were 0.73 and 0.74 in SNAC-S and 0.72 and 0.89 in SNAC-B. Conclusions and Implications: Our results suggest that the FIF tool is a valid tool to use for prediction of first-time injurious falls in community-living older adults. (C) 2020 AMDA - The Society for Post-Acute and Long-Term Care Medicine.
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| 10. |
- Gunnarsson, Anna-Karin
(författare)
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Patients with Hip Fracture : Various aspects of patient safety
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of the thesis was to investigate whether patient safety can be improved for patients with hip fracture by nutritional intervention and by pharmacological treatment with cranberry concentrate. Another aim was to describe the patients’ experience of involvement in their care. The thesis includes results from four studies that include both quantitative and qualitative design. Studies I and II were intervention studies with a quasi-experimental design, with intervention and comparison groups. Study III was a randomised, double-blind, placebo-controlled trial with intervention and control groups. Study IV took a qualitative approach.Study I showed that when patients with hip fracture received nutritional supplementation according to nutritional guidelines, from admission until five days postoperatively, fewer patients developed pressure ulcers. Study II showed that it is possible to objectively evaluate a short-term nutritional intervention through the nutritional biochemical marker IGF-1, as it was affected by a five-day high-energy regimen. The randomised controlled trial, Study III, showed that a short-term treatment from admission until five days postoperatively with cranberry as capsules does not seem to be useful in preventing positive urine cultures in female patients with hip fracture and a urinary catheter. Finally, Study IV showed that patients with hip fracture reported experiencing very little involvement in their nursing care, to the extent that fundamental aspects of nursing care went unfulfilled. Patients did not feel valued by the nurses and unbearable pain that affected rehabilitation was reported. Positive interactions with nurses, however, did encourage patients to be more active.It is possible for every nurse to improve patient safety at bedside when caring for patients with hip fracture. Simply by increasing caloric/energy intake, it is possible to prevent pressure ulcers. It is also important to involve patients in nursing care, since the patients have experienced low or almost no involvement in care. Nurses need to see each patient as a whole person with different wishes and needs. However, certain prerequisites have to be in place to give nurses the opportunity to increase patient safety at bedside for patients with hip fracture.
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